The dentist's role in recognizing childhood abuses: study on the dental health of children victims of abuse and witnesses to violence.

AIM: Up to today, little attention and training has been paid, in the Italian dental field, to a dramatically widespread problem, childhood abuse and neglect (CAN). Our research fits into a current of thought on alerting physicians, not only paediatricians, to the problem of abused children. Violence is often part of neglect and carelessness toward children, and it often also concerns their personal hygiene and health care. Aim of our study was to verify the hypothesis that dental neglect, intended as a specific form of neglect, is often associated to other types of neglect, and therefore it could represent an important sign in identifying childhood abuse and neglect situations. These were investigated through the comparison between a group of children with psychological disorder and a control group, as far as their dental health is concerned. Our results indicate that the abused children show: a significantly higher dental plaque index (p=.02); a higher gingival inflammation (p =.2); a higher number of untreated decays (p=.004); more evidences of neglect (p = .0002). Additionally, the abused subjects were less cooperative during dental visits (p=.0005). Our data support the hypothesis that the abused children in our group are, both under the hygiene point of view and access to treatment, more neglected by their caregivers.

Enhanced APOE2 transmission rates in families with autistic probands.

We have previously described linkage/association between reelin gene polymorphisms and autistic disorder. APOE also participates in the Reelin signaling pathway, by competitively antagonizing Reelin binding to APOE receptor 2 and to very-low-density lipoprotein receptors. The APOE2 protein variant displays the lowest receptor binding affinity compared with APOE3 and APOE4. In this study, we assess linkage/association between primary autism and APOE alleles in 223 complete trios, from 119 simplex Italian families and 44 simplex and 29 multiplex Caucasian-American families. Statistically significant disequilibrium favors the transmission of epsilon2 alleles to autistic offspring, over epsilon3 and epsilon4 (allele-wise transmission/disequilibrium test [TDT], chi2 = 6.16, 2 degrees of freedom [d.f.], P<0.05; genotype-wise TDT, chi2 = 10.68, 3 d.f., P<0.05). A novel epsilon3r allele was also discovered in an autistic child and his mother. Autistic patients do not differ significantly from unaffected siblings (allele-wise TDT comparing autistic patients versus unaffected sibs, chi2 = 1.83, 2 d.f., P<0.40, not significant). The major limitation of this study consists of our small sample size of trios including one unaffected sibling, currently not possessing the statistical power necessary to conclusively discriminate a specific association of epsilon2 with autism, from a distorted segregation pattern characterized by enhanced epsilon2 transmission rates both to affected and unaffected offspring. Our findings are thus compatible with either (a) pathogenetic contributions by epsilon2 alleles to autism spectrum vulnerability, requiring additional environmental and/or genetic factors to yield an autistic syndrome, and/or (b) a protective effect of epsilon2 alleles against the enhanced risk of miscarriage and infertility previously described among parents of autistic children.

Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) correspondence and conflicts with DSM-IV criteria in diagnosis of autism.

Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) are tests widely used for screening and diagnosis of autism. This study verified their correspondence and conflict with a diagnosis made with DSM-IV criteria. The sample consisted of 65 children, aged 18 months to 11 years. We found complete agreement between DSM-IV and CARS. We show that ABC does not distinguish individuals with autistic disorders from other cases of developmental disorders as well as CARS: the number of false negatives is high (46%) with ABC as opposed to 0% with CARS.

Oral manifestations in a group of young patients with anorexia nervosa.

Anorexia nervosa (AN) is an eating disorder (ED) identified using DSM-IV criteria. Eating disorders are occurring increasingly earlier in childhood and can lead to a series of oral manifestations. The aim of this study was to evaluate the correlation between stomatognathic lesions and eating disorders in 80 young patients (76 females and 4 males aged 9-18 years) with restricting or binge-eating/purging AN. The results confirm the close correlation between ED and oral lesions, the most common of which were dental erosion, dentinal hypersensitivity, the extrusion of amalgam restorations and xerostomia. The authors conclude by emphasising the importance of involving dentists in the diagnosis and treatment of ED.

Gastric electric activity assessed by electrogastrography and gastric emptying scintigraphy in adolescents with eating disorders.

BACKGROUND: Patients with eating disorders can refer to a variety of gastrointestinal symptoms, sometimes to justify reduced food intake and vomiting. The authors investigated whether adolescent patients with eating disorders and dyspeptic symptoms have altered gastric electric activity and abnormal gastric emptying as assessed respectively by electrogastrography and scintigraphy. METHODS: Twenty-eight patients (18 with anorexia and 10 with bulimia) and 16 healthy volunteers underwent electrogastrography; 20 of the 28 patients (14 with anorexia and 6 with bulimia) underwent gastric emptying scintigraphy. Electrogastrography with bipolar recording lasted 1 hour, 30 minutes before and after a standard meal. Before gastric emptying scintigraphy, patients fasted overnight; during testing, they ingested a solid meal labeled with technetium-99m sulfur colloid. The ratio of fasting to postprandial electrogastrographic variables was evaluated using the Wilcoxon matched-pair test. The Mann- Whitney test was used to compare absolute values for electrogastrographic data in each group. The Student paired t test was used to compare scintigraphic results expressed as percentage of gastric emptying at 60 minutes and as the gastric emptying time (T(1/2)). RESULTS: Patients with bulimia significantly differed from those with anorexia and control subjects regarding the amount of normal gastric electric activity and bradygastria, and from patients with anorexia only regarding tachygastria. These electrogastrographic variables did not differ significantly between patients with anorexia and control subjects. Gastric emptying time (T(1/2)) was significantly longer in patients with bulimia than in those with anorexia. CONCLUSIONS: Adolescent patients with bulimia who complain of dyspeptic symptoms have documentable abnormalities of gastric electric activity and emptying, whereas their counterparts with anorexia, probably owing to their shorter disease duration, do not.

Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children.

Autism is a biologically-heterogeneous disease. Distinct subgroups of autistic patients may be marked by intermediate phenotypes, such as elevated serotonin (5-HT) blood levels, potentially associated with different underlying disease mechanisms. This could lead to inconsistent genetic association results, such as those of prior studies on serotonin transporter (5-HTT) gene promoter variants and autistic disorder. Contributions of 5-HTT gene promoter alleles to 5-HT blood levels were thus investigated in 134 autistic patients and 291 first-degree relatives. Mean 5-HT blood levels are 11% higher in autistic patients carrying the L/L genotype, compared to patients with the S/S or S/L genotype; this trend is not observed in first-degree relatives. The probability of inheriting L or S alleles is significantly enhanced in patients with 5-HT blood levels above or below the mean, respectively (P < 0.05), but quantitative TDT analyses yield a non-significant trend (P = 0.10), as this polymorphism explains only 2.5% of the variance in 5-HT blood levels of autistic patients. In conclusion, 5-HTT gene promoter variants seemingly exert a small effect on 5-HT blood levels in autistic children, which largely does not account for hyperserotoninemia. Nonetheless, the inconsistent outcome of prior association studies could partly stem from a selection bias of hyper- or hypo-serotoninemic probands.

No association between the 4g/5G polymorphism of the plasminogen activator inhibitor-1 gene promoter and autistic disorder.

Plasmin, a serine protease, is involved in many physiologically relevant processes, including haemostasis, cellular recruitment during immune response, tumour growth, and also neuronal migration and synaptic remodelling. Both tissue-type and urokinase-type plasminogen activators can be efficiently inhibited by plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor of the serpin family. The human PAI-1 gene is located on chromosome 7q, within or close to a region that has been linked to autism in several linkage studies. Autism seems to be characterized by altered neuronal cytoarchitecture, synaptogenesis and possibly also cellular immune responses. We began addressing the potential involvement of the PAI-1 gene in autistic disorder with this linkage/association study, assessing transmission patterns of the 4G/5G polymorphism in the PAI-1 gene promoter that was previously shown to significantly affect PAI-1 plasma levels. No linkage/association was found in 167 trios with autistic probands, recruited in Italy and in the USA. We thus found no evidence that this polymorphism, or putative functionally relevant gene variants in linkage disequilibrium with it, confer vulnerability to autistic disorder.

Urinary mevalonate excretion rate in type 2 diabetes: role of metabolic control.

An increased cholesterogenesis has been described in obese dyslipidemic type 2 diabetic patients and in a small number of patients with poor glucose control. So far, it is not clear if increased cholesterogenesis in type 2 diabetes is related to the degree of glycemic control or depends on the commonly associated dyslipidemia or both. Therefore, the aim of the present study was to investigate the relationships among cholesterogenesis and degree of metabolic control in a group of non-obese normolipidemic type 2 diabetic patients. Fifty four (25 men and 29 postmenopausal women) non-obese type 2 diabetic patients with cholesterol and triglyceride plasma levels, respectively, below 6.40 and 2.85 mmol/l and 20 normal subjects matched for age and sex were studied. Endogenous cholesterol synthesis was evaluated by the determination of 24-h urinary mevalonate excretion (MVA). In the diabetic group the mean glycated hemoglobin was 8.47+/-2.2% (range 4.6-14.6%), the mean total cholesterol, triglycerides, HDL and LDL cholesterol were, respectively, 4.86+/-0.7, 1.64+/-0.5, 1.19+/-0.3 and 2.87+/-0.7 mmol/l. The mean 24-h MVA urine excretion rates were 1.41+/-0.3 micromol/24 h in control subjects and 1.66+/-0.7 micromol/24 h in diabetics (P=0.05). In diabetics, urinary mevalonate excretion was significantly correlated with glycated hemoglobin concentrations (HbA(1c)) (r=0.65; P=0.0001) and body mass index (BMI) (r=0.33; P=0.009). In the multivariate analysis both HbA(1c) and BMI were independent predictors of urinary mevalonate. These data demonstrate that lower the degree of blood glucose control, higher is the whole body cholesterol production even in the absence of overt dyslipidemia. In conclusion, the relationship between mevalonate excretion rate and glycated hemoglobin gives further weight to the importance of intensive blood-glucose control in diabetic disease and adds a new element to the list of potentially atherogenic factors strictly related to hyperglycemia in type 2 diabetic patients.

Carotid intima-media thickness in patients with Type 2 diabetes and hypercholesterolemia.

Both patients with Type 2 diabetes mellitus (T2DM) and with hypercholesterolemia have a more extensive and accelerated atherosclerosis with higher common carotid artery intima-media thickness (CIMT) values than the general population. The aim of this study was to compare the CIMT in polygenic hypercholesterolemia (HP; n=41: 30 females and 11 males, aged 52+/-15 yr) and in T2DM (n=43: 22 females and 21 males, aged 59+/-11 yr), with a duration of disease less than 5 yr and no evidence of coronary heart disease. A control group (C) of 40 sex- and age-matched healthy subjects was studied. We evaluated the CIMT on the far wall of the distal segment of the common carotid arteries on sites free of plaque. The mean of the CIMT measurements (Tmean; 9 on each side) and the maximal CIMT measured (Tmax) were used as the representative values for each subject. Tmax values were 0.96+/-0.2 mm and 0.82+/-0.2 mm in T2DM and HP, respectively, which were significantly higher than C (0.74+/-0.1 mm). Corresponding values of Tmean were 0.8+/-0.1 mm and 0.71+/-0.2 mm, both significantly higher than C (0.68+/-0.1 mm). In HP, both Tmax and Tmean values were positively correlated to age (p=0.0001 and p=0.0001, respectively), body mass index (BMI; p=0.05 and p=0.05, respectively), presence of hypertension (p=0.003 and p=0.0008, respectively) and fibrinogen (p=0.0009 and p=0.001, respectively); Tmean was also correlated to apolipoprotein B (ApoB; p=0.03). The multiple "stepwise" regression analysis revealed fibrinogen and age as the only significant determinants of Tmax and Tmean. In T2DM Tmax and Tmean were positively correlated to age only (p=0.04 and p=0.01, respectively). In conclusion, T2DM patients have a more accelerated atherosclerosis than subjects with HP. This is evident after a short duration of disease, probably for a longer latency period of disease and the presence of multiple risk factors.

Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder.

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.

Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.

Adenosine deaminase (ADA) plays a relevant role in purine metabolism, immune responses, and peptidase activity, which may be altered in some autistic patients. Codominant ADA1 and ADA2 alleles code for ADA1 and ADA2 allozymes, the most frequent protein isoforms in the general population. Individuals carrying one copy of the ADA2 allele display 15 to 20% lower catalytic activity compared to ADA1 homozygotes. Recent preliminary data suggest that ADA2 alleles may be more frequent among autistic patients than healthy controls. The present study was undertaken to replicate these findings in a new case-control study, to test for linkage/association using a family-based design, and to characterize ADA2-carrying patients by serotonin blood levels, peptiduria, and head circumference. ADA2 alleles were significantly more frequent in 91 Caucasian autistic patients of Italian descent than in 152 unaffected controls (17.6% vs. 7.9%, P = 0.018), as well as among their fathers. Family-based tests involving these 91 singleton families, as well as 44 additional Caucasian-American trios, did not support significant linkage/association. However, the observed preferential maternal transmission of ADA2 alleles, if replicated, may point toward linkage disequilibrium between the ADA2 polymorphism and an imprinted gene variant located in its vicinity. Racial and ethnic differences in ADA allelic distributions, together with the low frequency of the ADA2 allele, may pose methodological problems to future linkage/association studies. Direct assessments of ADA catalytic activity in autistic individuals and unaffected siblings carrying ADA1/ADA1 vs ADA1/ADA2 genotypes may provide stronger evidence of ADA2 contributions to autistic disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:784-790, 2000.

[The heart of anorexic adolescents]. / Il cuore nelle adolescenti anoressiche.

BACKGROUND: Anorexia nervosa (AN) is often associated with cardiac changes, such as thinning of the left ventricle (LV), reduction of LV mass, abnormalities of mitral valve function and systolic dysfunction. Some authors have reported QT interval prolongation and sudden death in these patients. METHODS: We studied 23 adolescent females, aged 14.7 +/- 2 years (mean +/- SD), with AN. Serum electrolytes, proteins and albumin were measured in all patients. Electrocardiogram, Doppler-echocardiogram and chest X-rays were also performed on the same day. Eighteen patients were also examined via indirect calorimetry (difference from basal metabolic rate) and 21 underwent dosage of thyroid hormones. RESULTS: The patients, who were of normal height (159 +/- 7.4 cm), were underweight (36 +/- 4.8 kg) and had a body mass index (BMI) of less than 19 (14.2 +/- 1.3). Serum electrolytes, proteins, albumin and chest X-rays were substantially normal in all patients; 74% of them showed reduction of FT3. The calorimetry was reduced (-27.1 +/- 10.6%) with the exception of one patient. Resting heart rate was 58 +/- 12 bpm. We found normal values for PR, QRS, QT (0.41 +/- 0.03 s1/2) and QTc intervals (0.40 +/- 0.03 s1/2) and QT dispersion (40.9 +/- 14.1 ms). Echocardiography showed a reduction in the dimensions of the interventricular septum (52% of patients), LV free wall (61%), left atrium (31%) and LV mass (61%). Fractional shortening was normal in all but one patient. In 61% of cases, there was mild or moderate pericardial effusion that was clinically silent and inversely related to BMI (r = -0.38, p 0.08, ns), to calorimetry (r = -0.56, p < 0.0055), to FT3 (r = -0.53, p < 0.05) and to sodium concentration (r = -0.43, p 0.04). CONCLUSIONS: Teen-agers with AN often show a reduction in LV thickness and mass, as well as clinically silent pericardial effusion that is inversely related to BMI, calorimetry, FT3 and sodium serum concentrations. We did not find any prolongation of QTc interval or of QT dispersion.

Use of the Parental Bonding Instrument to compare interpretations of the parental bond by adolescent girls with restricting and binge/purging anorexia nervosa.

The Parental Bonding Instrument (PBI) was administered to 62 adolescent female patients (mean age 14.3): 35 with restricting-type anorexia nervosa (RAN), and 27 with binge/purging-type anorexia nervosa (B/PAN) according to the DSM-IV criteria, all at onset and initial diagnosis. The PBI was also administered to a control group (55 subjects) and 22 patients with Crohn's disease or celiac disease. The three groups were matched for age and socioeconomic status. The RAN and B/PAN patients gave significantly different interpretations of the parental bond (PB): for the former, it was adequate with both parents, for the latter it was inadequate, especially with the father. The fact that these differences exist at the onset of anorexia prior to any possible effect of therapy suggests that its structure is determined by different family dynamics.

Relapsing gross haematuria in Münchausen syndrome.

A 10-year-old female with relapsing gross haematuria and Münchausen syndrome is reported, emphasizing the rarity of this situation in children and the difficult diagnostic pathway. A careful personality study of the patient and family members is absolutely necessary in order to proceed with diagnosis and successful treatment.