Family environment and attention-deficit/hyperactivity disorder in adopted children: associations with family cohesion and adaptability.

BACKGROUND: Positive family environments are crucial in promoting children's emotional and behavioural well-being, and may also buffer development of attention-deficit/hyperactivity disorder (ADHD). ADHD is highly heritable, but psychosocial factors in the family environment, particularly family cohesion and communication, may mediate genetic predispositions. The purpose of the current study is to examine the mediating influence of the adoptive family environment between pre-adoptive risk factors and youths' ADHD symptomatology at 14 years post adoption. METHODS: The data used in this study were obtained from the fourth wave of the California Long-Range Adoption Study (CLAS) (n = 449). Using structural equation modelling (SEM), family sense of coherence and family adaptability were tested as possible mediators between environmental and biological predictors and ADHD symptomatology. Predictors included birthweight, gender, age at adoption, adoption from foster care, transracial adoption status, ethnicity and having a previous diagnosis of ADHD. RESULTS: Results show that, while adoption from foster care is negatively associated with family functioning, higher family cohesion and adaptability mediate this influence on children's ADHD symptomatology. Older age of adoption directly predicts greater ADHD symptoms with no mediating influence of the family environment. CONCLUSIONS: The mediating influence of the family environment between children's risk factors and ADHD symptoms suggests that family intervention strategies may be helpful in improving adopted children's outcomes. Once children are adopted, targeting family communication patterns and dynamics may be an additional part of developing an evidence-based, post-adoption services toolkit.

Intraperitoneal insulin infusion improves the depletion in choline-containing phospholipids of lipoprotein B particles in type I diabetic patients.

Insulin-dependent diabetes mellitus (IDDM) is characterized by altered composition of atherogenic lipoproteins, especially a depletion in choline-containing phospholipids (PL) of apolipoprotein (apo) B lipoproteins (LpB). To determine the effects of continuous intraperitoneal (IP) insulin infusion (CIPII) on this qualitative lipoprotein abnormality, we compared lipoprotein profiles of 14 IDDM patients treated by continuous subcutaneous insulin infusion (CSII) and at 2 and 4 months after treatment with CIPII using an implantable pump. IDDM patients were in fair metabolic control and were compared with 14 healthy control subjects matched for sex, age, body mass index, and plasma lipids. The following parameters were studies: hemoglobin A1c (HbA1c), monthly blood glucose, daily insulin dose (units per kilogram per day), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, apo A-I, and apo B. Choline-containing PL were assessed in plasma and in apo B- and no-apo B-containing lipoprotein particles (LpB and Lp no B). As compared with the control group, plasma PL and LpB-PL were significantly lower in IDDM patients treated by CSII (2.95 +/- 0.26 v 3.30 +/- 0.45 mmol/L,P<.05, and 1.09 +/- 0.45 v 1.68 +/- 0.33 mmol/L,P<.01, respectively). No significant differences were observed for Lp no B lipid determinations between both groups. After initiation of CIPII, IDDM patients did not experience any significant changes in mean values for body mass index, HbA1c, and monthly blood glucose throughout the study. Daily insulin doses were identical to those observed before IP therapy. Lipid parameters remained unchanged in IDDM patients (TC, TG, HDL and LDL cholesterol, apo A-I, and apo B). A moderate but progressive elevation of plasma PL was noted, and after 4 months of CIPII, PL and LpB-PL levels were no longer significantly different between IDDM patients and controls. The increase in plasma and LpB choline-containing PL observed after 2 and 4 months of CIPII is not linked to changes in blood glucose control, body weight or daily insulin requirements. These changes may be related to the route of insulin administration, which may be accompanied by a reduction of lipoprotein lipase (LPL) activity and consequently a reduction of phospholipase activity. These results suggest that IP insulin delivery may be a more physiological route that increases the choline-containing PL content of LpB particles.

[Turner's syndrome and autoimmune dysthyroidism]. / Syndrome de Turner et dysthyroïdies auto-immunes.

The authors report a case of Turner's syndrome associated with Hashimoto's thyroiditis and present the various physiopathological hypotheses currently offered to explain the frequent association of an autoimmune pathology and a gonadal dysgenesis with an absence of X chromosome which is held responsible for autoimmunity. Is the chromosomal abnormality a factor predisposing to autoimmunity or does it result from a disturbance of the immune mechanism? Environmental factors, such as bacteria, viruses or some pollutants might be responsible for both the immune disorders and the chromosomal abnormality. The association of the two types of disease may also be accidental. In the present state of our knowledge, there is no answer to these questions.

The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes.

CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Lower-extremity arterial disease in diabetes mellitus due to chronic pancreatitis.

OBJECTIVE: To determine the prevalence of lower-extremity arterial disease and the sites of arterial obstruction in patients with pancreatic diabetes. PATIENTS AND METHODS: The retrospective study included 83 patients with diabetes due to chronic pancreatitis (age [m +/- SD] 54.5 +/- 9.5 yr, diabetes duration 9.7 +/- 7.4 yr) and 83 patients with idiopathic diabetes were carefully matched for sex, age, diabetes duration and treatment. They were screened for arteriopathy by segmental blood pressures and Doppler ultrasound, and for cardiovascular risk factors. The arterial lesions were classified as proximal (above-knee), distal (below-knee), and combined (both above- and below-knee). RESULTS: Lower extremity arterial disease occurred in 25.3% of pancreatitis patients and in 14.5% of idiopathic diabetes patients (p = 0.08). The sites of obstruction in both groups were similar; proximal obstruction: 4 vs 4 cases; distal: 10 vs 5 cases, combined: 7 vs 3 cases. The prevalence of arteriopathy increased with age and diabetes duration in both groups (p < 0.01). Total cholesterol, LDL cholesterol and apolipoprotein B were lower in the pancreatitis patients (p < 0.01); 92% of these were smokers vs 62% of idiopathic diabetes patients (p < 0.001). CONCLUSIONS: Arteriopathy, assessed by non-invasive tests, has the same prevalence and distribution in chronic pancreatitis and idiopathic diabetes patients, despite their different vascular risk factor profiles. This emphasizes the role of chronic hyperglycaemia and its duration in the pathogenesis of macroangiopathy in diabetic patients.

Lack of relationship between Lp(a) particle levels and albumin excretion rate in type 1 diabetic patients.

The excess risk of cardiovascular disease in Type 1 diabetes mellitus compared to non diabetic subjects is only partially explained by standard risk factors. Several studies suggest that Lp(a) concentrations are increased in Type 1 diabetes mellitus, but data are still controversial. Moreover, a high cardiovascular risk has been reported in diabetic patients with persistent proteinuria. Therefore, the aim of this study was to compare the Lp(a) particle levels in insulin-dependent diabetic patients with or without increased urinary albumin excretion. Cross-sectional study of Lp(a) plasma levels in a population of 140 insulin-dependent diabetic patients: 83 without increased proteinuria, 14 with borderline elevation of urinary albumin excretion, 27 with micro- and 16 with macro-proteinuria. Simultaneous determination of plasma lipids, fasting blood glucose and HbA1c was performed. The mean plasma Lp(a) concentrations and the distribution of the levels were comparable in all of the diabetic patient groups. No relationship existed between Lp(a) and HbA1c, fasting blood glucose or any lipid plasma levels. No influence of albumin excretion rate on Lp(a) levels was observed. These data provide no evidence of a specific contribution of Lp(a) particles to the increased morbidity and mortality from cardiovascular disease observed among patients with nephropathy.

Structure-affinity relationships in the gp41 ELDKWA epitope for the HIV-1 neutralizing monoclonal antibody 2F5: effects of side-chain and backbone modifications and conformational constraints.

The human monoclonal antibody, mAb 2F5, has broad HIV-1 neutralizing activity and binds a conserved linear epitope within the envelope glycoprotein gp41 having a core recognition sequence ELDKWA. In this study, the structural requirements of this epitope for high-affinity binding to mAb 2F5 were explored using peptide synthesis and competitive enzyme-linked immunosorbant assay (ELISA). Expansion of the minimal epitope to an end-capped, linear nonapeptide, Ac-LELDKWASL-amide, was sufficient to attain maximal affinity within the set of native gp41-sequence peptides assayed. Scanning single-residue alanine and d-residue substitutions then confirmed the essential recognition requirements of 2F5 for the central DKW sequence, and also established the importance of the terminal leucine residues in determining high-affinity binding of the linear nonapeptide. Further studies of side-chain and backbone-modified analogs revealed a high degree of structural specificity for the DK sequence in particular, and delineated the steric requirements of the Leu(3) and Trp(6) residues. The nine-residue 2F5 epitope, flanked by pairs of serine residues, retained a high affinity for 2F5 when it was conformationally constrained as a 15-residue, disulfide-bridged loop. However, analogs with smaller or larger loop sizes resulted in lower 2F5 affinities. The conformational effects of the gp41 C-peptide helix immediately adjacent to the N-terminal end of the ELDKWA epitope were examined through the synthesis of helix-initiated analogs. Circular dichroism (CD) studies indicated that the alpha-helical conformation was propagated efficiently into the LELDKWASL epitope, but without any significant effect on its affinity for 2F5. This study should guide the design of a second generation of conformationally constrained ELDKWA analogs that might elicit an immune response that mimics the HIV-neutralizing actions of 2F5.