Children have been found to be able to reason about quantitative relations, such as non-symbolic proportions, already by the age of 5 years. However, these studies utilize settings in which children were explicitly guided to notice the mathematical nature of the tasks. This study investigates children's spontaneous recognition of quantitative relations on mathematically unspecified settings. Participants were 86 Finnish-speaking children, ages 5–8. Two video-recorded tasks, in which participants were not guided to notice the mathematical aspects, were used. The tasks could be completed in a number of ways, including by matching quantitative relations, numerosity, or other aspects. Participants’ matching strategies were analyzed with regard to the most mathematically advanced level utilized. There were substantial differences in participants’ use of quantitative relations, numerosity and other aspects in their matching strategies. The results of this novel experimental setting show that investigating children's spontaneous recognition of quantitative relations provides novel insight into children's mathematical thinking and furthers the understanding of how children recognize and utilize mathematical aspects when not explicitly guided to do so.

Le diabete de type 2 est caracterise par deux anomalies physiopathologiques majeures : un deficit de l'insulinosecretion et une insulinoresistance. La perte du pic precoce en reponse au glucose caracterise le deficit de l'insulinosecretion, elle est responsable de l'hyperglycemie post-prandiale. L'hyperglycemie chronique est un determinant important des complications micro- et macrovasculaires du diabete de type 2. En effet, les donnees de l'UKPDS montrent que le controle glycemique (evalue par l'HbA1c) permet de prevenir et/ou de ralentir la survenue des complications vasculaires [1]. L'analyse des resultats de cette etude a permis de demontrer qu'une diminution de 1 % de l'HbA1c etait associee a une baisse de 35 % du risque de complications microvasculaires, et de 18 % du risque d'infarctus du myocarde. Si les parametres les plus communement utilises chez les patients diabetiques de type 2 sont la glycemie a jeun et l'HbA1c, celui de la glycemie post-prandiale semble tout aussi justifie dans le suivi et la demarche therapeutique. En effet, un certain nombre d'arguments physiopathologiques et epidemiologiques mettent en evidence le role deletere de l'hyperglycemie post-prandiale.

En ce debut du troisieme millenaire, le diabete de type 2 pose un veritable probleme mondial de sante publique, et les autorites de sante l'ont bien compris, en placant cette affection au rang des priorites. Ce probleme est lie a la « flambee epidemique » de la maladie. De 99 millions de patients atteints dans le monde en 1994, le nombre attendu etait de 157 millions en l'an 2000 et de 215 millions en 2010. Cette augmentation atteint tous les pays, industrialises ou non, et la France est concernee au meme titre que les autres pays. Le corollaire de cette flambee epidemique est l'explosion des complications coronaires et vasculaires qui la suivra une decennie plus tard. En effet, le risque de complications coronaires, d'accidents vasculaires cerebraux et de complications de l'arteriopathie obliterante des membres inferieurs est le double ou le triple chez les diabetiques de celui qui est observe dans la population generale.

UNLABELLED:Previous studies have failed to predict somatostatin analog response with somatostatin receptor scintigraphy in pituitary adenomas. In vitro studies have shown that the density of somatostatin receptors in pituitary tumors might be critical for octreotide response.METHODS:The density of somatostatin receptors was calculated in vivo combining the uptake index obtained from somatostatin receptor scintigraphy and the tumor volume obtained by MRI. The ratio of these two values, called density index (DI), was established in 32 of 37 consecutive patients with pituitary adenomas (11 had growth hormone-secreting adenomas, 4 thyroid-stimulating hormone-secreting and 17 nonfunctioning). It was compared with hormonal response, assessed in 15 secreting adenomas on growth hormone or thyroid stimulating hormone suppression (which was considered significant when it reached at least 50% of basal level), and with tumor shrinkage (which was considered significant when > or =20% of pretherapeutic value) in 12 secreting and 14 nonfunctioning adenomas.RESULTS:In agreement with previous reports, uptake index is not predictive of octreotide response. In contrast, DI predicts both hormonal suppression and tumor shrinkage (P = 0.009 and P = 0.0002, respectively) obtained with octreotide therapy. DI sensitivity, specificity and accuracy were 92% each, and a positive correlation was found between DI and the percentage of tumor shrinkage (r = 0.54, P = 0.004).CONCLUSION:The combination of scintigraphic and MRI data allows the computation of a DI for somatostatin receptors that points out patients who can profit from somatostatin analog treatment.

We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80–90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

Le diabete de type 2 est responsable d'une surmorbidite et d'une surmortalite cardiaques et vasculaires. L'hypertension arterielle represente un facteur de risque vasculaire associe, dont l'incidence est particulierement elevee chez les diabetiques de type 2 (20 a 50 %). L'hyperglycemie chronique est impliquee dans le developpement des complications vasculaires. Quelle est l'implication d'un controle tensionnel optimal sur la survenue de celles-ci ? A cet effet, trois etudes recentes d'intervention ont ete analysees : la United Kingdom prospective diabetic study (UKPDS), l'Hypertension optimal treatment (HOT) et l'Appropriate blood control in diabetes (ABCD). Ces etudes avaient toutes pour criteres de jugement la morbidite et la mortalite cardiovasculaires. L'analyse de ces etudes montre qu'il est possible d'obtenir un controle tensionnel optimal par un traitement medical intensif. S'il ne semble pas exister de superiorite d'une classe therapeutique par rapport a une autre pour equilibrer la pression arterielle, en revanche, l'obtention d'un bon equilibre se fait au prix d'une polymedication au cours du temps. Le controle optimal tensionnel permet de diminuer significativement le risque de survenue d'evenements lies au diabete, de mortalite liee au diabete, et de survenue d'evenements cardiovasculaires majeurs (infarctus du myocarde, accidents vasculaires cerebraux, deces d'origine cardiovasculaire). A la lumiere de ces donnees, les objectifs tensionnels proposes sont une pression arterielle diastolique inferieure ou egale a 80 mmHg et une pression arterielle systolique inferieure ou egale a 130-140 mmHg.

The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic treatment in a population of diabetic patients with chronic diarrhoea (defined as > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration, number of stools per day, and gastrointestinal symptoms) were noted. Autonomic neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group 1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/- 11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS), and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75 +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/- 2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P < 0.05). The prevalence of small intestinal bacterial overgrowth syndrome and gastrointestinal symptoms was not different in patients with and without autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5 g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of these patients. It is concluded that small intestinal bacterial overgrowth should be considered in case of chronic diabetic diarrhoea because of its frequency (43%), facility of diagnosis, and often successful treatment with antibiotics.

Relationships between glycaemic control, hypertension, and development of microangiopathy have been well documented in Type 1 (insulin-dependent) but not in Type 2 (non-insulin-dependent) diabetes mellitus. Therefore, we have investigated these relationships in a cohort of 64 Type 2 patients free of retinopathy (by angiofluorography), who were regularly followed until development of retinopathy or for at least 7 years as outpatients. Glycaemic control was assessed by 1 to 4 HbA1 determinations per year. Retinal status was monitored by annual angiofluorography. Nonproliferative retinopathy developed in 14 patients (cumulative incidence at 13 years: 29.8%) after a mean diabetes duration of 14.3+/-8.9 years (range 2-27). In multivariate analysis (Cox model), mean HbA1 during follow-up (p < 0.001), and hypertension at first examination (p = 0.09) were associated with the development of retinopathy, but age, sex, BMI, diabetes duration, smoking, and fasting blood glucose were not. The relative risk for developing retinopathy (RR) was 7.2 (IC 95%: 1.61-32.4) in patients with a mean HbA1 during follow-up above the median value of the cohort (8.3%) compared with patients with HbA1 during follow-up below this value. RR was 2.5 (IC 0.8-8) in patients with HbA1 at first examination above compared to below the median value (8.4%). RR was 3.0 (IC 0.9-10) in patients treated for hypertension at baseline compared to those without treatment. A sixfold increase in retinopathy prevalence was observed between patients with mean HbA1 in the highest or lowest quartile of mean HbA1 distribution during follow-up. This longitudinal study indicates a strong association between long-term glycaemic control and the development of diabetic retinopathy in Type 2 diabetes.

OBJECTIVEGiven the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours.DESIGNWe determined if GnRHR mRNA was expressed in gonadotroph tumours using RT‐PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of α, β‐FSH and β‐LH subunit (SU) genesSUBJECTSRNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry ( >10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high α‐SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects.RESULTSWe found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 α‐secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for β‐FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker.CONCLUSIONThe GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.

OBJECTIVEA multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH‐secreting and non‐functioning pituitary adenomas.SUBJECTS AND METHODSSomatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non‐functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty‐five patients were treated for 1 month with octreotide (300 μg daily). The therapeutic response was assessed on GH and IGF‐I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied.RESULTSFrom the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide‐induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non‐functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non‐functioning pituitary adenomas with expression of sst2 only.CONCLUSIONIn the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non–functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.

Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.

La découverte d'un adénome hypophysaire peut résulter de syndrome(s) d'hypersécrétion et/ou de déficits(s) antéhypophysaire(s) et/ou d'un syndrome tumoral, ou être fortuite. Une évaluation des fonctions hypophysaires, de l'acuité et du champ visuel et la réalisation d'une IRM ou au moins d'un scanner sont indispensables au diagnostic et à la décision thérapeutique: chirurgie pour la maladie de Cushing ; agonistes dopaminergiques pour les prolactinomes ; analogues de la somatostatine ou chirurgie pour les adénomes thyréotropes ; chirurgie et/ou analogues de la somatostatine et/ou radiothérapie pour l'acromégalie ; chirurgie complétée de radiothérapie pour la plupart des adénomes, voire expectative dans certains cas.