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Fil: Birochio, Diego Enrique. Universidad Nacional de Río Negro. Centro de Investigaciones y Transferencia de Río Negro. Río Negro; Argentina. Fil: Roldán, Virginia Alonso. Grupo de Investigación en Gestión Desarrollo Territorial y Ambiente (GesDTA), UTN Facultad Regional Chubut, Puerto Madryn, Chubut, Argentina. Fil: Camino, Micaela. EDGE, Sociedad Zoológica de Londres, Camden, Londres, Reino Unido. 5CECOAL-CONICET, Corrientes, Argentina Fil: Argoitia, Antonella. UNNE-CONICET, Corrientes, Argentina. Fil: Campos, Claudia M. Red de Ecología de Mamíferos de Tierras Secas. IADIZA (CONICET, UNCuyo, Gob. de Mendoza), Mendoza, Argentina Fil: Caruso, Nicolás. Grupo de Ecología Comportamental de Mamíferos, INBIOSUR-CONICET-UNS, Bahía Blanca, Argentina Fil: Eder, Elena B. Grupo de Estudios de Macroecología Marina (GEMMA), CESIMAR-CONICET, Puerto Madryn, Chubut, Argentina Fil: Baldi, Ricardo. Grupo de Estudio de Mamíferos Terrestres (GEMTE), IPEEC-CONICET, Puerto Madryn, Chubut, Argentina. Fil: Cappa, Flavio M. CIGEOBIO, UNSJ-CONICET, San Juan, Argentina Fil: Lassaga, M. Victoria. Natura International, Córdoba, Argentina. Fil: Olmedo, M. Luz. Programa de Conservación de los Murciélagos de Argentina (PCMA), Tucumán, Argentina Fil: Formoso, Anahí. Grupo de Estudio de Mamíferos Terrestres (GEMTE), IPEEC-CONICET, Puerto Madryn, Chubut, Argentina. Fil: D ́Agostino, Valeria C. Laboratorio de Mamíferos Marinos, CESIMAR- CONICET, Puerto Madryn, Chubut, Argentina. Fil: Udrizar Sauthier, Daniel. UNPSJB, Puerto Madryn, Chubut, Argentina. Fil: González Noschese, Camila S. Instituto de Investigaciones de Biodiversidad Argentina (PIDBA), UNT- CONICET, San Miguel de Tucumán, Argentina. Fil: Juárez, Cecilia P. Centro de Ecología y Biodiversidad del Chaco Argentino (CEBiCA), Facultad de Recursos Naturales, UNaF, Formosa, Argentina. Fil: Degrati, Mariana. Laboratorio de Mamíferos Marinos, CESIMAR- CONICET, Puerto Madryn, Chubut, Argentina. Fil: Iglesias, Martín. Grupo de Estudios sobre Biodiversidad en Agroecosistemas, Depto. BBE, FCEyN, UBA, CABA, Argentina. Fil: Coelho, Lorena. IIBCE, MEC, Uruguay. Fil: Drouville, Ailín Sosa. UNCO-Río Negro, Argentina. Fil: Priotto, José W. Grupo de Investigaciones en Ecología Poblacional y Comportamental (GIEPCO), Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente (ICBIA), UNRC-CONICET, Río Cuarto, Córdoba, Argentina. Mammals are key components of biodiversity mediating ecosystem functions, mainly because ofthe diversity of forms and functions of this group. Understanding and making explicit the role of mammalsunderpinning Nature’s Contributions to People (NCP) or directly contributing to human well-being wouldhelp to in uence policy formulation towards sustainable development and nature conservation. Througha workshop held at the XXXII Jornadas Argentinas de Mastozoología and subsequent collaborative work,we compiled information related to Mammal’s Contributions to People in Argentina (MCP-Arg) based onparticipants’ interpretation of the available literature and their eld experience. Argentinian mammalscontribute to 12 of the 18 de ned NCPs. We derived numerous MCP-Arg from studies that focused mainly onecological processes and conservation, revealing an information gap in MCP-Arg description, quanti cation,and mapping. All taxa contribute similarly to the overall contributions, highlighting the importance ofpreserving mammal diversity. Conservation should also be framed at the local community rather thanregional scales, aiming to preserve ecological functioning and contributions to human well-being, especiallywithin regulation contributions. Our results show destructive feedback between threats and habitat-relatedcontributions, with habitat degradation being the greatest threat to mammalian contributions and habitatmaintenance the most threatened one. Our research indicates that a substantial amount of knowledge about MCP-Arg is available through narratives and interpretations. Considering the NCP approach to mammalia Considering the NCP approach to mammalian research, we can make signi cant contributions to both mammal conservation and human well-being RESUMEN.CONTRIBUCIONES POTENCIALES AL BIENESTAR HUMANO DE LOS MAMÍFEROSEN ARGENTINA. Debido a su diversidad de formas y funciones, los mamíferos son componentes clave dela biodiversidad y cumplen importantes funciones ecosistémicas. Para formular políticas que permitan undesarrollo sostenible y la conservación de la naturaleza, es fundamental comprender y explicitar el papel de losmamíferos en sustentar las Contribuciones de la Naturaleza a las Personas (CNP). Durante un taller realizadoen las XXXII Jornadas Argentinas de Mastozoología y un posterior estudio colaborativo, hemos recopiladoinformación relacionada con las CNP de mamíferos en Argentina (CMP-Arg) en base a la interpretaciónde la literatura disponible y la experiencia de campo. En la Argentina, los mamíferos contribuyen en 12 delas 18 CNP de nidas. Deducimos numerosas CMP-Arg de estudios centrados principalmente en procesosecológicos y de conservación, que muestran un vacío de información en cuanto a descripción, cuanti cación ymapeo de CMP-Arg. Todos los taxones realizan aportes similares a las contribuciones totales, lo que destaca laimportancia de preservar la diversidad de mamíferos. Los esfuerzos de conservación deben enmarcarse no soloa escala regional, sino también a escala local, con el objetivo de preservar las CNP. Nuestros resultados hanmostrado una asociación entre amenazas y contribuciones relacionadas con el hábitat: la degradación de esteha sido la principal amenaza para las contribuciones y su mantenimiento la contribución más amenazada.Nuestra investigación muestra que una cantidad importante de conocimiento sobre CMP-Arg está disponiblea través de narrativas y representaciones sociales. Mediante la implementación del enfoque del CNP enla investigación mastozoológica, podemos hacer aportes signi cativos tanto para la conservación de losmamíferos como para el bienestar humano.

Context Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS. Objective This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI). Methods We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years. Results MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 +/- 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007). Conclusions The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.

Purpose The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents. Methods A survey was conducted among Italian children and adolescents aged 4–18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values. Results The survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18–24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains. Conclusions Our results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.

Objective Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Conclusions Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Exotic herbivores have detrimental effects on the ecosystems where they are introduced, at the level of plant communities and ecosystem processes. The native guanaco Lama guanicoe and the exotic feral donkey Equus asinus coexist in Ischigualasto Provincial Park. We quantified food availability in a plant community in the park during the wet and dry seasons, analyzed diet composition of both herbivores (by microhistological analysis of feces), and assessed the relationship between diet and plant availability and the overlap between donkey and guanaco diets. In both seasons, shrub species represented the most abundant cover type in the area, whereas grasses were the lowest plant cover during the wet season and almost non-existent in the dry season. The diet of the exotic donkey showed a high intake of grasses, and the trophic niche breadth did not change along the year. The guanaco’s diet was based on the most abundant food resources (shrubs), which constituted at least 60% of the diet; it was less diverse during the dry season. The diets of donkey and guanaco showed high overlap during the dry season. We can assume, at least during the dry season, the existence of a potential competition between guanaco and donkey, which may be higher if the donkey density increases. Fil: Reus, Maria Laura. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cappa, Flavio Martín. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Andino, Natalia del Pilar. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Campos, Valeria Evelin. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: de Los Rios, Claudia. Universidad Nacional de San Juan; Argentina Fil: Campos, Valeria Evelin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina

Craniopharyngioma (CP) is the most common intracranial non-glial tumour observed in pediatric age. Although histologically benign and amenable to surgical treatment, its location and relation with vital nervous and vascular structures makes the feasibility of a radical resection difficult even in the microneurosurgery era. Beside the difficulties experienced when performing tumour resection, post-operative complications, such as endocrinological imbalance, represent another point that makes CP total excision a challenge. In order to avoid such complications, some authors have suggested to renounce to radical resection and to rely on post-operative radiation therapy to minimise the risk of residual tumour progression.We report our experience with 52 children and adolescents operated on for CP at the Department of Pediatrics, Section of Pediatric Neurosurgery, Catholic University Medical School, Rome, between January 1985 and December 2002. The study included 14 children5 years old (five less than 2 years of age), 25 between 6 and 10 years old, and 13 more than 10 years old. The most common presenting signs were related to endocrinological imbalance (35 cases), increased intracranial pressure (32 cases), and to a lesser extent, visual compromise (17 cases). Concerning location, CP was intrasellar in three cases; sellar/suprasellar with prominent prechiasmatic growth in 24 cases; retrochiasmatic/3rd ventricular in 14 cases, and giant (with an extension into the middle and/or posterior cranial fossae) in 11 cases. The tumour was managed by means of a single surgical approach in 47 cases and with a two-stage operation in the remaining five cases. In 11 cases of intrasellar or intra/suprasellar midline location, the first surgical approach was done through the transsphenoidal route (which represented the first step of a staged operation in five instances); in the remaining 41 patients, craniotomy was the first surgical procedure. Radical tumour resection was achieved in 40 cases, subtotal (only small tumour remnants adherent to the carotid arteries, 3rd ventricle floor or visual pathways) in nine, and only partial in the remaining three casesHistology demonstrated the adamantinous variant in all cases. Two surgical deaths were recorded in this series (both following a transsphenoidal approach): one secondary to uncontrollable intra-operative bleeding from the carotid artery, and the other to fulminating bacterial meningoencephalitis. Morbidity included endocrinological disturbances, namely hypopituitarism and diabetes insipidus, in more than 80% of cases, worsening of pre-operative visual deficit in six cases, and transitory neurological deficits in five cases. One late death was recorded 2 years after surgery, secondary to electrolytic imbalance although favoured by a major head trauma with subacute subdural haematoma. Nine recurrences occurred 1-8 years after surgery (three true recurrences, and six re-growths of incompletely resected tumours) that required re-operation. Twelve patients underwent radiotherapy, six after an initially incomplete tumour resection and six following relapse. One patient presented with a malignant thalamic glioma 8 years after radiotherapy. At long-term follow-up, all survivors showed good clinical condition, even though approximately 60% relied on hormone replacement, and some patients presented obesity. Diabetes insipidus has subsided in about 80% of the cases; visual deficits improved or remained stable, whereas post-operative neurological deficits subsided in all but one patient.In our experience, radical resection of CP represented the first and almost unique treatment modality. Although not insignificant, post-operative mortality and morbidity do not seem to represent a major contraindication in attempting a radical tumour resection whenever possible. On the other hand, extensive hypothalamic involvement should suggest a less aggressive attitude.

The survival of children with cancer has grown considerably in recent years resulting in a marked increase of endocrine complications. increasingly recognized problems are metabolic syndrome and diabetes mellitus.We critically analysed the most recent literature about the prevalence and molecular mechanisms of metabolic dysregulation and long-term cardio-metabolic risk in this population.Hypothalamic irradiation determines growth hormone deficiency and hypogonadism; moreover it is able to disrupt the appetite regulating centre leading to hyperphagia and progressive obesity. These conditions determine an insulin resistant state, contributing to the development of metabolic syndrome and diabetes mellitus. Irradiation and/or chemotherapy may lead to an insulin secretory defect through a direct damage of pancreatic beta cells.Metabolic syndrome and diabetes mellitus represent increasingly recognized long-term complications of childhood cancer treatment. The different impact of insulin resistance and secretory defects on the onset and progression of metabolic syndrome and diabetes mellitus remains unclear.

Prader-Willi syndrome (PWS) is a disabling condition characterized by hypotonia, hyperphagia, obesity, short stature, delayed or absent puberty, and mental retardation. The syndrome complex was first described in 1956 by Dr. Andrea Prader and colleagues [1]. In the 1980s, a characteristic genetic defect was identified involving deletion of paternal alleles at chromosome 15q11-13 [2-6]. This occurs by deletion of alleles on the paternal copy of chromosome 15q, an absent paternal chromosome 15q with maternal disomy, or, rarely, by mutations of the imprinting center of chromosome 15q. The estimated population prevalence of PWS is 1 in 15,000 live births.

The following paper by Professor GiovanniNeri and colleagues was originally published in 1988, American Journal of Medical Genetics 30:287–299. This paper represented a seminal work at the time of publication as it not only reported a new family with a disorder that had been called the “gigantism-dysplasia syndrome”, but also suggested naming the condition the Simpson-Golabi-Behmel syndrome. This eponym has clearly stood “the test of time”, and that designation is now widely accepted. This paper is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We report on another family with the so-called "gigantism-dysplasia syndrome", an X-linked condition characterized by pre-and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi-Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al. in 1975 and by Behmel et al. in 1984. Therefore, we suggest that this entity be designated the Simpson-Golabi-Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X-linked encephalo-tropho-schisis syndrome.

Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear.To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males.Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups :or ≥13·5 years.Pubertal PWS patients showed an arrest of pubertal development. Patients13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH.PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis).

A diagnosis of KBG syndrome was made in six unrelated patients. They presented with slight mental retardation, macrodontia, and skeletal abnormalities. Microcephaly, short stature, facial anomalies, and syndactylies were also noted. The diagnostic criteria of the KBG syndrome are discussed.

No data are available about the risk of thyroid disturbance after exposure to low-dose radiation due to the use of cardiac catheterization in the first years of life.To determine the risk of functional and morphological thyroid abnormalities in a homogeneous cohort of patients who underwent diagnostic low-dose radiation for heart catheterization during the first 18 months of life.Fifty-five patients, submitted to cardiac catheterization during the first 18 months of life, underwent evaluation of the thyroid function and structure after a median period of 13 yr since the first radiation exposure. Sixty-eight unexposed controls matched for age and sex, underwent the same protocol. Twenty-two patients were then re-evaluated after a median period of 22 yr.Thyroid function resulted normal in both patients and controls. The prevalence of small thyroid nodules and inhomogeneous structures in ultrasound study was not augmented in irradiated patients compared to controls. No thyroid tumors or reduced thyroid volume were observed.Neither functional nor morphological disorders of the thyroid gland were demonstrated after a period up to 24 yr in patients exposed to diagnostic ionizing radiation for cardiac catheterization during the first 18 months of life.

Although pharmacological GH stimulation tests are still considered the gold standard for GH deficiency (GHD) diagnosis, they are burdened by poor specificity. The majority of children diagnosed as having GHD show normal GH responses when re-tested at the end of growth, thus questioning the initial diagnosis. We evaluated the concordance between IGF-I levels and GH responses to provocative tests.We analyzed 105 GHRH plus arginine tests, 79 arginine tests, and 124 clonidine tests performed in 192 short children. IGF-I levels ≤-2SD score (SDS) were considered suggestive for high likelihood of GHD. The percentage of positive and negative results for each test was determined and compared with IGF-I levels, clinical follow-up and response to therapy.In children with IGF-I-2SDS the arginine test showed a concordance rate of 6.9%, the clonidine test of 28.6%, and GHRH plus arginine test of 70%. In children with IGF-I≤-2SDS the concordance was 96.1%, 85.7%, and 46.4%, respectively. The overall concordance was 66.7% for GHRH plus arginine, 42.7% for clonidine, and 27.8% for arginine tests.Our results suggest that GHRH plus arginine test provides the best concordance with the assessment of IGF-I levels thus suggesting that the combination of the two procedures may significantly reduce the need of a second provocative test.

Metabolic characteristics and rate of progression to overt Type 2 diabetes (T2D) in low-risk European obese children are not well documented. Aim of the study was to investigate differences in insulin sensitivity and secretion in Italian obese children and youngsters with pre-diabetes.Ninety-six obese children and youngsters with pre-diabetes, pair-matched with individuals with normal glucose tolerance (NGT) were included in the present study. Participants were screened by oral glucose tolerance. Pre-diabetes was classified as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined IFG-IGT. Homeostasis model assessment of insulin resistance (HOMA-IR), 2-h insulin, insulin sensitivity index (ISI) and disposition index (DI) were calculated to estimate fasting, peripheral and whole body insulin sensitivity and capacity of pancreatic islets to compensate for lower insulin sensitivity, respectively. One-way analysis of variance was used to compare groups.Eleven subjects had IFG (11.5%), 79 IGT (82.3%), 6 combined IFG-IGT (6.3%). Individuals with IFG showed the highest HOMA-IR (p=0.0007), those with IGT the highest 2-h insulin (p0.0001), those with IFG-IGT the lowest ISI (p0.0001), with severely reduced DI (p=0.0003). Compared with NGT, DI was 60% lower in those with IFG-IGT.IFG is linked primarily to fasting insulin resistance, IGT to peripheral insulin resistance. IFG-IGT is hallmarked by reduced whole body insulin sensitivity and an additional severe defect in DI. Further longitudinal studies are needed to understand whether the different categories of pre-diabetes in European obese adolescents represent real pre-diabetic alterations.

X-linked adrenoleukodystrophy/adrenomieloneuropathy (ALD/AMN) is a progressive neurodegenerative disorder due to mutations in the ABCD1 gene encoding the ABC transporter ALDP. Mutations in ALDP impair peroxisomal β-oxidation of very long chain fatty acids (VLCFA), resulting in elevated levels of VLCFA in plasma, nervous system, and adrenals. Lorenzo's oil, combined with VLCFA- poor diet, normalizes plasma VLCFA within 1 month, but it does not prevent the progression of pre-existing neurological symptoms. No previous study analyzed the effect of Lorenzo's oil therapy on adrenal function.To investigate short-term effects of Lorenzo's oil, combined with VLCFA- poor diet, on adrenal function of AMN patients with early subclinical signs of adrenal failure.Seven AMN subjects underwent VLCFA-restricted diet combined with Lorenzo's oil (45 ml/day po), without steroid therapy, for 6 months.All patients had elevated ACTH at baseline, and a significant reduction was evident after 6 months (median ACTH at baseline: 1300 pg/ml, range: 720- 2100; median ACTH at 6 months: 186 pg/ml, range: 109-320, p: 0.0156). Cortisol was normal both at baseline and after 6 months. VLCFA dropped in all patients during the 6- month follow-up, and no patient required glucocorticoid replacement therapy.Adrenal insufficiency in ALD/AMN is probably due to a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of the adrenal cell membrane functions. In an early phase, Lorenzo's oil therapy may be able to improve VLCFA clearance and restore a normal ACTH receptor activity, and hypoadrenalism may be potentially reversible.

This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

A series of 121 human breast tumors was screened for point mutations in exons 5 through 8 of the p53 gene, by SSCP analysis. On the same tumor samples, the S-phase index (SPI) was determined by the incorporation of BUdR in fresh tissue. p53 mutations were observed in 29% of the cases. The frequency of point mutations for the individual exons was: exon 5, 10.0%; exon 6, 9.9%; exon 7, 7.1% and exon 8, 5.5%. Two mutations detected by SSCP were confirmed by sequencing the p53 cDNA. The presence of a p53 mutation, irrespective of its location, correlates (p = 0.003) with a high SPI. This association appears to primarily reflect mutations in exon 5 (p = 0.0002) and exon 6 (p = 0.05), since mutations in exons 7 and 8 failed to show any association. These results indicate that mutations in the p53 gene identify highly proliferating tumors, and that the position of the p53 mutation may have different effects upon the proliferative activity of tumor cells in vivo.

A systematic study of primay human breast tumor DNA demonstrated that three proto-oncogenes or regions of the genome (c-myc, int-2, and c-erbB2) are frequently amplified and that there is loss of heterozygosity (LOH) on chromosomes 1p(37%), 1q(20%), 3p(30%), 7(41%), 11p(20%), 13q(30%), 17p(49%), 17q(29%), and 18q(34%). Specific subsets of tumors can be defined based on the particular collection of mutations they contain. For instance, LOH on chromosomes 11p, 17p, and 18q frequently occurs in the same tumor

Two girls with central precocious puberty (CPP) associated with hypothalamic hamartoma (HH) and non classical form of congenital adrenal hyperplasia (NCAH), are reported. Case 1. The first patient, who showed at age around 4 years the onset of CPP, was submitted in view of some organic lesion to magnetic resonance (MRI) of the brain which documented the presence of HH. The remarkable acceleration of bone age (BA) advanced of 3 SD and some clinical signs of hyperandrogenism suggested the coexistence of NCAH, proved by adrenocorticotropic hormone (ACTH) test and molecular analysis. She resulted carrier of partial 21-hydroxylase deficiency. Case 2. In the second girl with CPP, aged 6.5 years, the remarkable advancement (4 SD) of bone age (BA) alerted to adrenal involvement. ACTH stimulation test and molecular analysis showed NACH due to 21-hydroxylase deficiency. Brain MRI, performed mainly for severe headache, showed the presence of HH. Yearly brain MRI to monitor HH dimensions and neurological examination with EEG, in order to exclude anomalies referable to gelastic epilepsy are advisable, in both cases. The authors' observation emphasizes the need to be careful in young patients with CPP, with fast progression of pubertal development and remarkable BA advancement. The association of CPP with HH and NCAH should be considered, performing not only MRI of the brain, but also ACTH test, beside LHRH test for the diagnosis of CPP. At the authors' knowledge this association has not been reported so far. Further observations are needed to understand if this rare combination is occasional or genetically determined.

This population-based study examines whether dietary intake in middle-aged Italian women is influenced by alcohol drinking habits. The 499 participants were interviewed using a dietary history questionnaire designed to investigate alcohol consumption. Mean intake of total and non-alcohol energy increased progressively within categories of increasing alcohol consumption (less than 5, 5-19, 20-39, 40+ g/day). Mean body weight and Quetelet index (kg/m2), however, decreased with increasing alcohol consumption. Once the disparities in energy intake were reduced by computing intake densities, the data suggest that moderate and heavy drinkers have dietary habits similar to those of abstainers or light drinkers. These findings were confirmed by multiple linear regression analyses in which the confounding effects of age, place of residence, occupation, and Quetelet index were taken into account. Increasing alcohol consumption appeared associated only with a modest decrease in the intake of fibre, beta-carotene, and vitamin C. These findings do not support the hypothesis that the observed protection from coronary artery disease among moderate drinkers is related to a chronic reduction in the intake of carbohydrates and fat, at least in middle-aged women.

Late cytokinetic changes of the colonic crypt epithelium after radiation therapy were investigated. A monoclonal antibody to bromodeoxyuridine (anti-BrdU MAb) was used in tissue specimens previously incubated with BrdU to show S-phase cells by immunohistochemical technique. Endoscopic rectal biopsies were taken from 30 patients previously treated with radiotherapy for gynaecological cancer and from 50 patients with comparable but untreated neoplasms, as controls. Number and height distribution of S-phase cells were evaluated by dividing each crypt column into 5 equal longitudinal compartments. No statistically significant differences were found in total Labelling Index (LI) between controls and irradiated mucosa, whereas LI per crypt compartment, percentage of labelled compartments and percentage of BrdU-positive cells in the middle and superficial portions of the crypt were significantly higher in patients submitted to radiation therapy. This kinetic abnormality corresponds to a progressive shift of the major zone of DNA synthesis to the upper third of the crypt as a late reaction to radiation and represents an early step in the histogenesis of colorectal cancer. These results lend support to the view that there is a higher risk of colorectal carcinoma after pelvic irradiation.