Ganglionic Eminence Anomalies and Coexisting Cerebral Developmental Anomalies on Fetal MR Imaging: Multicenter-Based Review of 60 Cases.

BACKGROUND AND PURPOSE: The ganglionic eminences are transient fetal brain structures that produce a range of neuron types. Ganglionic eminence anomalies have been recognized on fetal MR imaging and anecdotally found in association with a number of neurodevelopmental anomalies. The aim of this exploratory study was to describe and analyze the associations between ganglionic eminence anomalies and coexisting neurodevelopmental anomalies. MATERIALS AND METHODS: This retrospective study includes cases of ganglionic eminence anomalies diagnosed on fetal MR imaging during a 20-year period from 7 centers in Italy and England. Inclusion criteria were cavitation or increased volume of ganglionic eminences on fetal MR imaging. The studies were analyzed for associated cerebral developmental anomalies: abnormal head size and ventriculomegaly, reduced opercularization or gyration, and abnormal transient layering of the developing brain mantle. The results were analyzed using χ2 and Fisher exact tests. RESULTS: Sixty fetuses met the inclusion criteria (21 females, 24 males, 15 sex unknown). Thirty-four had ganglionic eminence cavitations (29 bilateral and 5 unilateral), and 26 had increased volume of the ganglionic eminences (19 bilateral, 7 unilateral). Bilateral ganglionic eminence cavitations were associated with microcephaly (P = .01), reduced opercularization, (P < .001), reduced gyration (P < .001), and cerebellar anomalies (P = .01). Unilateral ganglionic eminence cavitations were not significantly associated with any particular feature. Bilateral increased volume of the ganglionic eminences showed an association with macrocephaly (P = .03). Unilateral increased volume was associated with macrocephaly (P = .002), abnormal transient layering (P = .001), unilateral polymicrogyria (P = .001), and hemimegalencephaly (P < .001). CONCLUSIONS: Ganglionic eminence anomalies are associated with specific neurodevelopmental anomalies with ganglionic eminence cavitations and increased ganglionic eminence volume apparently having different associated abnormalities.

MR Imaging Diagnosis of Diencephalic-Mesencephalic Junction Dysplasia in Fetuses with Developmental Ventriculomegaly.

Diencephalic-mesencephalic junction dysplasia is a rare malformation characterized by a poorly defined junction between the diencephalon and the mesencephalon, associated with a characteristic butterfly-like contour of the midbrain (butterfly sign). This condition may be variably associated with other brain malformations, including callosal abnormalities and supratentorial ventricular dilation, and is a potential cause of developmental hydrocephalus. Here, we have reported 13 fetuses with second-trimester obstructive ventriculomegaly and MR features of diencephalic-mesencephalic junction dysplasia, correlating the fetal imaging with available pathology and/or postnatal data. The butterfly sign can be clearly detected on axial images on fetal MR imaging, thus allowing for the prenatal diagnosis of diencephalic-mesencephalic junction dysplasia, with possible implications for the surgical management of hydrocephalus and parental counseling.

Neuroimaging Changes in Menkes Disease, Part 1.

Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease.

Ricinus communis treatment of denture stomatitis in institutionalised elderly.

This study compared the effectiveness of Ricinus communis (RC) with Nystatin (NYS) and Miconazole (MIC) in the treatment of institutionalised elderly with denture stomatitis (DS). They (n = 30) were randomly distributed into three groups: MIC, NYS or RC. Clinical and mycological evaluations were performed prior to the use of the antifungal (baseline) and repeated after 15 and 30 days of treatment. The sample was clinically examined for oral mucosal conditions. Standard photographs were taken of the palate, and the oral candidiasis was classified (Newton's criteria). Mycological investigation was performed by swabbing the palatal mucosa, and Candida spp. were quantified by counting the number of colony-forming units (cfu mL⁻¹). The clinical and mycological data were analysed, respectively by Wilcoxon and Student's t-test (α = 0.05). Significant improvement in the clinical appearance of DS in the MIC and RC groups was observed between the 1st and 3rd collections (MIC - P = 0.018; RC - P = 0.011) as well as between the 2nd and 3rd collections (MIC - P = 0.018; RC - P = 0.011). Neither groups showed a statistically significant reduction in cfu mL⁻¹ at any time. Although none of the treatments decreased the cfu mL⁻¹, it was concluded that Ricinus communis can improve the clinical condition of denture stomatitis in institutionalised elderly patients, showing similar results to Miconazole.

Clinical and genetic study of 46 Italian patients with primary lymphedema.

Primary lymphedema is characterized by altered morphological development of lymphatic vessels causing fluid accumulation in interstitial spaces. In familial forms, it is primarily transmitted as a dominant Mendelian trait with heterozygous mutations in genes involved in lymphangiogenesis. We used PCR and direct sequencing to analyze the region of the fms-related tyrosine kinase 4 (FLT4) gene encoding the "tyrosine-kinase domain" and the single exon of the forkhead box C2 (FOXC2) gene in 46 Italian probands with primary lymphedema, 42 of whom had familial forms. We identified 12 mutations in 12 patients (12/46, 26%), six in the FLT4 gene and six in the FOXC2 gene. Most of the mutations (9/12, 75%) were new, and none were identified in 100 healthy subjects or listed in the NCBI dbSNP. A clear relation emerged between genotype and phenotype because 4/5 (80%) probands with onset at birth showed FLT4 mutations and 4/5 (80%) probands without distichiasis and with FOXC2 mutations had an amino-acid substitution outside the forkhead domain. Besides the allelic heterogeneity shown by unique mutations in each proband, the absence of mutations in almost 75% of familial cases of primary lymphedema also suggests genetic heterogeneity.

Pro-atherogenic postprandial profile: meal-induced changes of lipoprotein sub-fractions and inflammation markers in obese boys.

BACKGROUND AND AIMS: Obesity is a pro-atherogenic condition and postprandial lipoprotein profile and circulating cytokines changes may contribute to promote the process. The aim of this study is to investigate postprandial metabolic response, lipoprotein oxidation and circulating cytokine levels, after the ingestion of two different meals with different fat/carbohydrate ratio. METHODS AND RESULTS: Ten prepubertal obese boys consumed two meals with the same energy and protein content but with a different carbohydrate to fat ratio: 1) moderate fat (MF): 61% carbohydrate, 27% fat; 2) high fat (HF): 37% carbohydrate, 52% fat. The AUC of glucose and insulin were significantly (p < 0.05) lower after the HF meal. HF meal was followed by a significant decrease in the cholesterol carried in the HDL fractions, while cholesterol in the small, dense LDL and in the VLDL particles increased, as compared to baseline (p < 0.05 for all). No differences were found in the cholesterol distribution after the MF meal. Moreover, HDL-C concentration was lower (p < 0.05) at 300 min after HF vs. MF meal. Oxidized LDL (ox-LDL) concentration increased after the HF meal but not after the MF meal [9.3(2.2) vs 1.8(2.2)% from baseline, P < 0.02)]. A positive association (r > 0.3, P < 0.05) was observed between the densest LDL particles and the ox-LDL plasma levels. A reduction of IL-6 was found at 120 min after the MF [-23.3(5.5) vs -8.4(3.8)% from baseline, P < 0.05)] compared with the HF meal. CONCLUSION: A simple change of ≈25% of energy load from fat to carbohydrate in a meal significantly improves postprandial pro-atherogenic factors in obese boys.

Noncarious cervical lesions and their association with toothbrushing practices: in vivo evaluation.

OBJECTIVES: This pilot study aims to investigate the prevalence of noncarious cervical lesions (NCCLs) in a student population at the Faculty of Dentistry of Araçatuba­UNESP and to assess the potential relation between buccal hygiene habits and the presence and number of NCCLs. METHODS: This study was conducted with a sample of 58 young volunteers (15 men and 43 women; mean age, 23.6 ± 1.8 years and 22.3 ± 2.4 years, respectively). The research was divided into three steps: 1) clinical assessment; 2) oral-hygiene practices self-report questionnaire; and 3) analysis of toothbrush filament deformations. After the clinical exam the participants were divided into two groups, a control group (without NCCLs) and a test group (NCCLs), according to NCCL presence. The data were statistically analyzed with SPSS 16.0 software, using t-test, χ2, Fisher exact test, and Spearman correlation. RESULTS: NCCLs were present in 53% of the subjects. The presence of NCCLs was marginally statistically associated with age (p=0.15) and proportionally more prevalent in male (80%) subjects (p=0.01). NCCLs were more concentrated in the posterior-superior quadrant (93%) in both the right (90%) and left (55%) sides of the mouth. The direct rank correlation was presented between presence of NCCLs and toothbrush firmness; and between number of NCCLs and age and force applied during toothbrushing. CONCLUSION: Within the limitations of this pilot study, the use of medium and hard toothbrushes and greater force applied during toothbrushing might contribute to the development and/or aggravation of NCCLs.

Joubert syndrome with bilateral polymicrogyria: clinical and neuropathological findings in two brothers.

Joubert syndrome (JS) is characterized by hypotonia, ataxia, developmental delay, and a typical neuroimaging finding, the so-called "molar tooth sign" (MTS). The association of MTS and polymicrogyria (PMG) has been reported as a distinct JS-related disorder (JSRD). So far, five patients have been reported with this phenotype, only two of them being siblings. We report on one additional family, describing a living child with JS and PMG, and the corresponding neuropathological picture in the aborted brother. No mutations were detected in the AHI1 gene, the only so far associated with the JS + PMG phenotype. Moreover, linkage analysis allowed excluding all known gene loci, suggesting further genetic heterogeneity.

Early diagnosis and treatment of celiac disease in type 1 diabetes. A longitudinal, case-control study.

OBJECTIVES: Subjects with type 1 diabetes mellitus (DM) are at increased risk to develop celiac disease (CD). However, most of the published investigations on the association between type 1 DM and CD are cross-sectional ones. In this paper, longitudinal data are presented on the effects of gluten-free diet (GFD) on growth and metabolic control in children and adolescents with type 1 DM screened for CD. METHODS: Clinical records of 27 patients with type 1 DM+CD (7% of a population of 385 subjects with type 1 DM) were reviewed. The following variables were considered at the diagnosis of CD (T0) and after 24 (T24) and 48 (T48) months of GFD according to the length of available follow-up: weight, height, body mass index (BMI), Hb and HbA1c levels and per kg/day dose of insulin. Forty-three patients with type 1 DM alone, matched for sex, age and duration of diabetes were chosen as controls. RESULTS: In patients with type 1 DM+CD, mean (SD) age at type 1 DM diagnosis was 8 (3.3) years. Median time interval between diagnosis of type 1 DM and of CD was 1.8 years (range 0.1-23.9 years). At T0 (n = 23), height and BMI z-score, HbA1c levels and daily insulin dose were comparable in type 1 DM+CD and in control subjects. Mean Hb concentration was significantly lower in subjects with type 1 DM+CD (12.6 (1.3) vs. 13.3 (0.7) g/dl, p < 0.05). At T24 (n = 22) and T48 (n = 16), no difference was detectable in height, BMI, HbAlc and insulin dose and also Hb concentration was comparable in both groups. CONCLUSIONS: This study shows that, at diagnosis of CD, screened subjects with type 1 DM had only minor signs of malnutrition and metabolic disturbances were uncommon. Dietary treatment of CD can allow a growth and diabetes control comparable with subjects with diabetes alone.

Posttraumatic cerebral infarction in patients with moderate or severe head trauma.

OBJECTIVE: To evaluate the frequency, types, and location of posttraumatic cerebral infarction, to assess if secondary cerebral insults were associated with cerebral infarction, and to determine if cerebral infarction affected patients' outcome. METHODS: We based diagnosis of cerebral infarction on review of brain CT scans. We assessed frequency of secondary cerebral insults, including intracranial hypertension, cerebral hypoperfusion, systolic hypo- and hypertension, arterial blood oxygen desaturation, hypocapnia, and hyperthermia, using clinical charts. We used the Glasgow Outcome Scale to evaluate outcome at 6 months after trauma. RESULTS: Of the 89 patients included, a total of 28 cerebral infarctions were found in 17 cases (19.1%). Infarctions were territorial in 23 (82.1%) and watershed in 5 (17.9%) cases. Territorial infarctions were localized to the middle cerebral artery (n = 9, 32.1%), lenticulostriate arteries (n = 6, 21.4%), posterior cerebral artery (n = 3, 10.7%), anterior cerebral artery (n = 3, 10.7%), thalamoperforating arteries (n = 1, 3.6%), and basilar artery (n = 1, 3.6%) territories. Watershed infarctions were in the boundary (n = 4, 14.3%) and terminal (n = 1, 3.6%) zones. Intracranial hypertension was the only independent variable predicting cerebral infarction (odds ratio [OR] 13.3; 95% CI 2.8 to 62.6). At 6 months after trauma, there was a lower proportion of patients with good outcome among patients with cerebral infarction vs patients without (23.5 and 61.1%; p = 0.005). Cerebral infarction was the only independent predictor of 6-month outcome (OR of good outcome 0.19, 95% CI 0.06 to 0.66). CONCLUSIONS: The risk of developing posttraumatic cerebral infarction may be higher in patients with intracranial hypertension than in those without. Patients with posttraumatic cerebral infarction may be at increased risk of residual disability.

Screening of coeliac disease in north Italian children with type 1 diabetes: limited usefulness of HLA-DQ typing.

AIM: To determine the contribution of HLA-DQA1* and HLA-DQB1* genes to the risk of coeliac disease (CD) in a cohort of children with type 1 diabetes mellitus (T1DM) from northern Italy. METHODS: Three hundred and fifty-seven children with T1DM, attending the Childhood Diabetes Unit of the University of Verona, have been regularly tested for serum IgA endomysial antibodies (EMA). All patients with positive EMA underwent small bowel biopsy to confirm the diagnosis of CD. HLA typing was performed in subjects with T1DM and CD, and in a control group of 79 EMA-negative patients with T1DM. RESULTS: Of the 357 patients tested, 25 (7%) had CD. The frequency of HLA-DQA1*0501-DQB1*0201 (T1DM + CD 68% vs T1DM 62%) and of DQA1*0301-DQB1*0302 (T1DM + CD 40% vs T1DM 35%) haplotypes, between T1DM patients with and without CD, was statistically comparable. A trend towards a reduction of the risk of CD (p = 0.055, OR: 0.22, CI 0.05: 1.04) was observed in patients with T1DM (28% vs T1DM + CD 2%) who did not carry either the HLA-DQA1*0501-DQB1*0201 or the DQA1*0301-DQB1*0302 haplotype. CONCLUSION: A high prevalence of HLA-DQA1* and -DQB1* susceptibility haplotypes for CD was observed both in EMA-negative diabetics and in those with associated CD. The implementation of screening programmes of CD in a T1DM population, based on the identification of HLA susceptibility haplotypes, seems to be of limited usefulness. Serial serologic screening of diabetic patients remains the advisable strategy.

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy: absence of sequence variability.

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Distribution of food intake as a risk factor for childhood obesity.

OBJECTIVE: The purpose of our study was to assess the relationship between nutrient intake, partitioning of food intake, parents' overweight and adiposity in a group of children. SUBJECTS: 530 7-11-year-old children: 278 males, 252 females. METHODS: Energy intake, nutrient intake and percentage distribution of the intake of energy among the different meals were assessed by means of diet history. Body composition was obtained by measuring skinfold thickness. RESULTS: We identified the relationship between the children's adiposity and their parents' body mass index (BMI) mother: r=0.12, P<0.01; father: r=0.13; P<0.01), carbohydrate (r=-0. 15, P<0.001) and fat intake (r=0.14, P<0.002), and the proportion of energy taken at dinner (r=0.1, P<0.05). A multiple regression analysis was run with a stepwise procedure using relative adiposity as the dependent variable and parents' BMI, dinner intake (percentage of energy intake), EI/BMR ratio (an index of energy intake validity), and sex (dummy variable) as independent variables. All the independent variables, except percentage of fat intake, were included in the final model. The equation was able to explain approximately 19% (R=0.44, P<0.001) of inter-individual fat mass percentage variability. CONCLUSIONS: Diet composition did not contribute to explain the children's adiposity when the parents' overweight (BMI) was taken into account. However, the percentage distribution of the intake of energy among the different meals, particularly at dinner, contributed to explain inter-individual variance of fatness in children of both sexes. International Journal of Obesity (2000)24, 75-80

Hypoglycaemia in children with type 1 diabetes mellitus.

Hypoglycaemia is a frequent acute complication of IDDM and is usually defined as a blood glucose level below 3.0 mmol/l. Hypoglycaemia stimulates several neuroendocrine responses, such as secretion of glucagon, adrenaline, growth hormone and cortisol, which are generally increased during this phenomenon. The true prevalence of hypoglycaemia is not known. Studies of the epidemiology of severe hypoglycaemia give prevalences ranging from 2.7 to 85.7 episodes per 100 patients per year. The major risk factor for severe hypoglycaemia is hypoglycaemia unawareness, which occurs particularly in patients with type 1 diabetes of long duration and in those with a history of frequent episodes of hypoglycaemia. The first step in the management of hypoglycaemia is to check blood glucose and to treat hypoglycaemia on the basis of symptoms. Hypoglycaemia requires urgent treatment with a fast-acting carbohydrate or, if severe, with parenteral glucagon or intravenous glucose. Prevention measures should be instituted to prevent subsequent episodes, particularly in younger children with hypoglycaemic seizures or when seizures are recurrent.

The role of nutrition in prevention of complications in insulin-dependent diabetes mellitus.

Nutrition management is an integral part of overall diabetic treatment that includes insulin, physical activity, emotional support and guidance. The aim of the present study was to evaluate a dietary approach in line with the recommended dietary allowances in terms of protein, total and saturated fat, carbohydrates as well as fibre and polyunsaturated fatty acid. A correct dietary approach may help to prevent and to reduce to a minimum any risk of hyperglycaemia, hypoglycaemia and important long-term complications such as obesity, hyperlipidaemia and hypertension, and at the same time normal growth development.

Operative management of deep endometriosis infiltrating the uterosacral ligaments.

STUDY OBJECTIVE: To describe and assess the efficacy of laparoscopic surgical treatment for patients with pain and deep endometriosis located on the uterosacral ligaments. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred ten consecutive women with deep endometriosis infiltrating uterosacral ligaments. INTERVENTION: Operative laparoscopic management of endometriosis. MEASUREMENTS AND MAIN RESULTS: Improvement was reported in 82.3% (70/85) of patients with severe dysmenorrhea and was considered satisfactory in 82.8% (58/70). Improvement also occurred in 88.2% (75/85) of women with deep dyspareunia, and was considered satisfactory in 88.0% (66/75). CONCLUSION: Provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of painful symptoms related to deep endometriosis infiltrating uterosacral ligaments. (J Am Assoc Gynecol Laparosc 6(1):31-37, 1999)