Search

To clarify the physiological role of Na(+)-D-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(-/-) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(-/-) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(-/-) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose-free diet. In wild-type mice, passage of D-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(-/-) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2. [ABSTRACT FROM AUTHOR]

The purpose of the study was to estimate the burden to families of raising a child with attention-deficit/hyperactivity disorder (ADHD). Data were drawn from a longitudinal sample recruited in western Pennsylvania. When participants were between 14 and 17 years old, parents completed a questionnaire assessing economic burden over the course of raising their children. Domains of economic burden to families included direct costs related to child's behaviors (excluding treatment expenses) and indirect costs related to caregiver strain. On average, participants with ADHD incurred a total economic burden over the course of child development that was more than five times greater compared to youths without ADHD (ADHD = $15,036 per child, Control = $2,848 per child), and this difference remained significant after controlling for intellectual functioning, oppositional defiant symptoms, or conduct problems. Parents of participants with ADHD were more likely to have changed their job responsibilities or been fired and reported lower work efficiency. The current evaluation of economic burden to individual families extends previous estimates of annual societal cost of illness (COI) of ADHD. Our rough annual estimate of COI for ADHD in children and adolescents is $124.5 billion (2017 US Dollars). Findings underscore the need for interventions to reduce the costly dysfunctional outcomes in families of children with ADHD.

Objectives: We examined the association of parent training (PT)-related factors with therapeutic success in the Treatment of Severe Childhood Aggression (TOSCA) study. Our aims were (1) to evaluate demographic and clinical characteristics as predictors of parent attendance and engagement in PT and (2) to examine the associations of parent attendance and engagement in PT with study-targeted child behavior outcomes (i.e., attention-deficit/hyperactivity disorder [ADHD] and disruptive behavior symptoms). TOSCA was a randomized clinical trial evaluating the effect of placebo versus risperidone when added to PT and psychostimulant for childhood ADHD with severe aggression., Methods: Data for 167 parents and children 6-12 years old with ADHD, oppositional defiant disorder (ODD) or conduct disorder, and severe physical aggression were examined. Analyses used generalized linear models., Results: Most parents (72%) attended seven or more of nine sessions. The average parental engagement, that is, the percentage of PT elements fully achieved across participants and sessions, was 85%. The average therapist rating of goal completion was 92%. Parents of non-white and/or Hispanic children (p = 0.01) and children with lower intelligence quotient (p = 0.02) had lower PT attendance; parents with lower family incomes (p = 0.01) were less engaged. Attendance and engagement predicted better scores on the primary child behavior outcomes of disruptive behavior (Nisonger Child Behavior Rating Form Disruptive Behavior Total) and ADHD and ODD symptoms, adjusting for baseline severity., Conclusions: When the clinical picture is sufficiently severe to warrant prescribing an atypical antipsychotic, PT is feasible for families of children with ADHD and co-occurring severe aggression. The promotion of attendance and engagement in PT is important to enhance clinical outcomes among this challenging population. Methods for overcoming barriers to participation in PT deserve vigorous investigation, particularly for those with low family income, non-white race, Hispanic ethnicity, or when children have lower cognitive level.

Objective: Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory., Methods: A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone)., Results: At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83)., Conclusions: Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

Objectives: Previous "Treatment of Severe Childhood Aggression" (TOSCA) reports demonstrated that many children with severe physical aggression and attention-deficit/hyperactivity disorder (ADHD) responded well to two randomized treatments (parent training [PT]+stimulant+placebo = Basic vs. PT+stimulant+risperidone = Augmented) for 9 weeks. An important clinical question is whether these favorable outcomes are maintained over longer times., Methods: Clinical responders to the 9-week trial (n = 103/168), defined as Clinical Global Impressions (CGI)-Improvement of much/very much improved plus substantial reduction in parent ratings of disruptiveness, were followed another 12 weeks (21 weeks total) while remaining on blinded treatment. Outcome measures included Clinical Global Impressions scale, Nisonger Child Behavior Rating Form (NCBRF), other parent/teacher-rated scales, laboratory tests, clinician ratings of abnormal movement, and other adverse events (AEs)., Results: Parent ratings of problem behavior showed minimal worsening of behavior from end of the 9-week acute trial (expected from regression to the mean after selecting best responders), but outcomes at Extension endpoint were meaningfully improved compared with acute study baseline. As expected, outcomes for Basic and Augmented treatment did not differ among these children selected for good clinical response. During Extension, more Augmented subjects had elevated prolactin; there were no clinically confirmed cases of tardive dyskinesia. Delayed sleep onset was the most frequent Basic AE. We also conducted a last-observation-carried-forward analysis, which included both nonresponders and responders. We found that, at the end of Extension, Augmented subjects had more improvement than Basic subjects on the NCBRF Positive Social subscale (p = 0.005; d = 0.44), the Antisocial Behavior Scale Reactive Aggression subscale (p = 0.03; d = 0.36), and marginally so on the Disruptive Behavior Total subscale (p = 0.058; d = 0.29, the primary outcome)., Conclusions: The medium-term outcomes were good for the participants in both treatment groups, perhaps because they were selected for good response. When nonresponders were included in ITT analyses, there was some indication that Augmented surpassed Basic treatment.

Objective: The purpose of this study was to examine the satisfaction of families who participated in the Treatment of Severe Childhood Aggression (TOSCA) study., Methods: TOSCA was a randomized clinical trial of psychostimulant plus parent training plus placebo (basic treatment) versus psychostimulant plus parent training plus risperidone (augmented treatment) for children with severe physical aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder. Parents completed a standardized Parent Satisfaction Questionnaire (PSQ)., Results: Of the 168 families randomized, 150 (89.3%) provided consumer satisfaction data. When they were asked if they would join the study again if they had the option to repeat, 136 (91%) said "yes," 11 (7%) said "maybe," and one (<1%) said "no." When asked if they would recommend the study to other parents with children having similar problems, 147 (98%) said "yes" and 3 (2%) said "maybe." Between 71% (rating one aspect of the Parent Training) and 96% (regarding the diagnostic interview) endorsed study procedures using the most positive response option. Asked if there were certain aspects of the study that they especially liked, 64 (43%) spontaneously reported parent training. Treatment assignment (basic vs. augmented) and responder status were not associated with reported satisfaction. However, responder status was strongly associated with parent confidence in managing present (p<0.001) and future (p<0.005) problem behaviors., Conclusions: These findings indicate high levels of satisfaction with TOSCA study involvement and, taken together with previous pediatric psychopharmacology social validity studies, suggest high levels of support for the research experience. These findings may inform research bioethics and may have implications for deliberations of institutional review boards., Trial Registry: Treatment of Severe Childhood Aggression (The TOSCA Study), NCT00796302, clinicaltrials.gov .

Adolescents with attention deficit/hyperactivity disorder (ADHD) are at an increased risk for substance use but the pathways through which this risk emerges are insufficiently understood. Tobacco, alcohol, and marijuana outcomes were compared between adolescents diagnosed with ADHD in early childhood (N = 113) and demographically similar controls (N = 65). Participants were assessed from age 5 until age 18. A comprehensive history of adolescent substance use was compiled for each participant and growth in ADHD and conduct disorder (CD) were modeled as they related to substance use outcomes. Results indicated that when compared with controls, adolescents with ADHD were more likely to try cigarettes, initiate alcohol use at early ages, and smoke marijuana more frequently. Furthermore, adolescents with ADHD were 4 to 5 times more likely than controls to escalate to heavy cigarette and marijuana use after trying these substances once. Adolescents with ADHD who escalated to heavy use patterns were more likely to display early cigarette use and marked problems with family members, but displayed fewer peer problems. There was evidence of baseline effects (latent intercept, measured at age 5) for both ADHD and CD on substance use outcomes. Furthermore, growth in ADHD symptoms accounted for much of the growth in CD symptoms, and consequently, escalating CD symptoms in childhood (latent slope) were viewed as a mediator of the relationship between ADHD and cigarette and marijuana use. Maternal drinking in early childhood was the strongest predictor of early adolescent alcohol use. These findings are discussed with respect to the role of ADHD in the development of adolescent risk outcomes.

Objective: Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested., Method: One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n = 84) or PT, STIM, and risperidone (Augmented treatment; n = 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n = 124) or conduct disorder (n = 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale., Results: Compared with Basic treatment (PT + STIM [44.8 ± 14.6 mg/day] + placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT + STIM [46.1 ± 16.8 mg/day] + risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p = .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p = .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p = .01). Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score ≤2, 70% for Basic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor., Conclusions: Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: http://clinicaltrials.gov, unique identifier: NCT00796302., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

With a novel antibody against the rat Na(+)-D-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and prevented by testosterone treatment. In the renal BBM vesicles, the rSGLT1-independent uptake of [(14)C]-α-methyl-D-glucopyranoside was similar in females and males, suggesting functional contribution of another Na(+)-D-glucose cotransporter to glucose reabsorption. Since immunoreactivity of rSGLT2-Ab could not be detected with certainty in rat extrarenal organs, the SGLT2 protein was immunocharacterized with the same antibody in wild-type (WT) mice, with SGLT2-deficient (Sglt2 knockout) mice as negative control. In WT mice, renal localization of mSGLT2 protein was similar to that in rats, whereas in extrarenal organs neither mSGLT2 protein nor mSglt2 mRNA expression was detected. At variance to the findings in rats, the abundance of mSGLT2 protein in the mouse kidneys was male dominant, whereas the expression of mSglt2 mRNA was female dominant. Our results indicate that in rodents the expression of SGLT2 is kidney-specific and point to distinct sex and species differences in SGLT2 protein expression that cannot be explained by differences in mRNA.

In Chinese hamster ovary cells expressing rabbit sodium-dependent glucose transporter (rbSGLT1) protein kinase A (PKA) activators (forskolin and 8-Br-cAMP) stimulated alpha-methyl D-glucopyranoside uptake. Kinetic analysis revealed an increase in both V(max) and affinity of the transport. Immunohistochemistry and biotinylation experiments showed that this stimulation was accompanied by an increased amount of SGLT1 localized into the plasma membrane, which explains the higher V(max) of the transport. Cytochalasin D only partly attenuated the effect of forskolin as did deletion of the PKA phosphorylation site of SGLT1 in transient transfection studies. Experiments using an anti-phosphopeptide antibody revealed that forskolin also increased the extent of phosphorylation of SGLT1 in the membrane fraction. These results suggested that regulation of SGLT1 mediated glucose transport involves an additional direct effect on SGLT1 by phosphorylation. To evaluate this assumption further, phosphorylation studies of recombinant human SGLT1 (hSGLT1) in vitro were performed. In the presence of the catalytic subunit PKA and [(32)P] ATP 1.05 mol of phosphate were incorporated/mol of hSGLT1. Additionally, phosphorylated hSGLT1 demonstrated a reduction in tryptophan fluorescence intensity and a higher quenching by the hydrophilic Trp quencher acrylamide, particularly in the presence of D-glucose. These results indicate that PKA-mediated phosphorylation of SGLT1 changes the conformation of the empty carrier and the glucose carrier complex, probably causing the increase in transport affinity. Thus, PKA-mediated phosphorylation of the transporter represents a further mechanism in the regulation of SGLT1-mediated glucose transport in epithelial cells, in addition to a change in surface membrane expression.

Context: There is mounting evidence of neurodevelopmental alterations implicating the prefrontal cortex (PFC) and basal ganglia in children with attention-deficit/hyperactivity disorder (ADHD). The brain undergoes substantive structural and functional changes with a differential timing between brain regions during development from childhood to adolescence. In vivo phosphorus 31 magnetic resonance spectroscopy ((31)P MRS) is a noninvasive neuroimaging approach that is sensitive in assessing developmental changes of overproducing/pruning of synapses., Objective: To provide support for a developmental mechanism targeting a bottom-up dysfunction of the basal ganglia impairing the fine-tuning of prefrontal functions in ADHD., Design: Cross-sectional study., Setting: Pittsburgh, Pennsylvania, and the surrounding areas., Participants: Thirty-one psychostimulant-naive children with ADHD (mean [SD] age, 8.1 [1.2] years; range, 6.1-10.0 years) and 36 healthy control subjects (mean [SD] age, 8.1 [1.3] years; range, 6.1-10.4 years)., Main Outcome Measure: Membrane phospholipid (MPL) precursor levels (ie, phosphomonoesters that are anabolic metabolites of MPL) were assessed in the PFC and basal ganglia as well as in 4 other brain regions using in vivo (31)P MRS., Results: Lower bilateral MPL precursor levels in the basal ganglia and higher MPL precursor levels in the inferior parietal region (primarily right side) were noted in the children with ADHD as compared with healthy control children. There was a group x age interaction in the PFC and inferior parietal region, with relatively older psychostimulant-naive children with ADHD showing significantly lower PFC and higher inferior parietal MPL precursor levels. No differences between groups were noted in the superior temporal, posterior white matter, or occipital regions., Conclusion: Though based on cross-sectional data, these results are suggestive of possible progressive, nonlinear, and sequential alterations implicating a bottom-up developmental dysfunction in parts of the cortico-striato-thalamo-cortical network in ADHD.

The predictive validity of symptom criteria for different subtypes of ADHD among children who were impaired in at least one setting in early childhood was examined. Academic achievement was assessed seven times over 8 years in 125 children who met symptom criteria for ADHD at 4-6 years of age and in 130 demographically-matched non-referred comparison children. When intelligence and other confounds were controlled, children who met modified criteria for the predominantly inattentive subtype of ADHD in wave 1 had lower reading, spelling, and mathematics scores over time than both comparison children and children who met modified criteria for the other subtypes of ADHD. In some analyses, children who met modified criteria for the combined type had somewhat lower mathematics scores than comparison children. The robust academic deficits relative to intelligence in the inattentive group in this age range suggest either that inattention results in academic underachievement or that some children in the inattentive group have learning disabilities that cause secondary symptoms of inattention. Unexpectedly, wave 1 internalizing (anxiety and depression) symptoms independently predicted deficits in academic achievement controlling ADHD, intelligence, and other predictors.

After decades of conflicting studies, the relation of coffee drinking to coronary artery disease (CAD) risk remains unresolved. Using Cox proportional-hazards models with 5 covariates, 127,212 subjects who supplied baseline data at voluntary health examinations from 1978 to 1985 were studied. Subsequently, 8,357 subjects were hospitalized for CAD. Coffee drinking was unrelated to CAD risk in 58,888 never smokers, but in ex-smokers and current baseline smokers, daily coffee intake was associated with higher CAD risk. This disparity was generally consistent in stratified subgroups. In conclusion, this relation of coffee consumption to increased CAD risk only in smokers could be explained by incomplete control for smoking, by other traits of smokers, or by an adverse biologic interaction of a coffee ingredient with smoking effect on CAD.

Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for adverse outcomes such as substance abuse and criminality, particularly if they develop conduct problems. Little is known about early predictors of the developmental course of conduct problems among children with ADHD, however. Parental psychopathology and parenting were assessed in 108 children who first met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for ADHD at 4-7 years old. When demographic variables and baseline ADHD and conduct problems were controlled, maternal depression predicted conduct problems 2-8 years following the initial assessment, whereas positive parenting during the structured parent- child interaction task predicted fewer future conduct problems. These findings suggest that maternal depression is a risk factor, whereas early positive parenting is a protective factor, for the developmental course of conduct problems among children with ADHD., (Copyright 2006 APA, all rights reserved.)

The product of gene RSC1A1, named RS1, is involved in transcriptional and posttranscriptional regulation of sodium-d-glucose cotransporter SGLT1, and removal of RS1 in mice led to an increase of SGLT1 expression in small intestine and to obesity (Osswald C, Baumgarten K, Stümpel F, Gorboulev V, Akimjanova M, Knobeloch K-P, Horak I, Kluge R, Joost H-G, and Koepsell H. Mol Cell Biol 25: 78-87, 2005). Previous data showed that RS1 inhibits transcription of SGLT1 in LLC-PK1 cells derived from porcine kidney. A decrease of the intracellular amount of RS1 protein was observed during cell confluence, which was paralleled by transcriptional upregulation of SGLT1. In the present study, the subcellular distributions of endogenously expressed RS1 and SGLT1 were compared in LLC-PK1 cells and human embryonic kidney (HEK)-293 cells using immunofluorescence microscopy. RS1 was located at the plasma membrane, at the entire trans-Golgi network (TGN), and within the nucleus. Treatment of LLC-PK1 cells with brefeldin A induced rapid release of RS1 from the TGN, and confluence of LLC-PK1 cells was accompanied by reduction of nuclear location of RS1; 84-90% of subconfluent cells and 5-34% of confluent cells contained RS1 in the nuclei. This suggests that confluence-dependent transcriptional inhibition by RS1 is partially regulated by nuclear migration. Furthermore, we assigned SGLT1 to microtubule-associated tubulovesicular structures and dynamin-containing parts of the TGN. The data indicate that RS1 inhibits the dynamin-dependent release of SGLT1-containing vesicles from the TGN.

This multi-voxel, phosphorus magnetic resonance spectroscopy ((31)P MRS) study examined the prefrontal cortex (PFC), basal ganglia (BG) and superior temporal (ST) region in 10 children with attention-deficit/hyperactivity disorder (ADHD) and 15 healthy controls. ADHD patients had lower PFC and BG phosphomonoester (PME) levels compared to healthy children. No differences were noted in the ST. These deficits in membrane phospholipid (MPL) precursor levels suggest reduced mass of cellular MPLs due to a possible underdevelopment of neuronal processes and synapses in ADHD.

A link exists between alcohol intake and increased blood pressure (BP), with many studies showing increased hypertension prevalence in heavy drinkers. The harmful and beneficial effects of alcohol can confound the study of the long-term risks of alcohol-related hypertension. We therefore studied cardiovascular sequelae separately in heavy drinkers, light drinkers, and abstainers among 127,212 subjects with BP and alcohol intake ascertained at 1978 to 1985 health examinations. Subsequent cardiovascular end points included mortality risk, hospitalization risk, and outpatient diagnosis of hypertension. Analyses were performed for all subjects and stratified by 5 alcohol-drinking categories (from never drinkers to >or=3 drinks/day). With <120/80 mm Hg as the referent, Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for 3 higher BP categories (120 to 129/80 to 84, 130 to 139/85 to 89, and >or=140/90 mm Hg). The covariates were age, gender, race, body mass index, education, and smoking. The risk of all outcomes was progressively higher for increasing BP categories, with a similarly increased risk for abstainers, light drinkers, and heavy drinkers. The interaction tests for alcohol and BP were not statistically significant for the mortality and hospitalization outcomes. Interpretation was limited by an inability to separate subjects with increased BP from alcohol consumption from those with other etiologies. In conclusion, the data indicate that the risks of hypertension are similar regardless of the amount of alcohol consumption.

Assessing impairment is an explicit component of current psychiatric diagnostic systems. A brief parent and teacher rating scale for assessing impairment was developed and studied using attention deficit hyperactivity disorder (ADHD) as an exemplar disorder. The psychometric properties of the Impairment Rating Scale (IRS) were measured in 4 samples. Two included ADHD and matched comparison children and the other 2 a school sample. Overall, IRS ratings exhibited very good temporal stability. They correlated with other impairment ratings and behavioral measures and displayed evidence of convergent and discriminant validity. The IRS was highly effective in discriminating between children with and without ADHD. Evidence that the parent and teacher IRS accounted for unique variance beyond ratings of ADHD symptoms is also presented. The scale is brief, practical, and in the public domain. The results of the studies and implications for the assessment of impairment are discussed.

Background: Little is known about the predictive validity of hyperkinetic disorder (HKD) as defined by the Diagnostic Criteria for Research for mental and behavioral disorders of the tenth edition of the International Classification of Diseases (ICD-10; World Health Organization, 1993), particularly when the diagnosis is given to younger children., Methods: The predictive validity of HKD was evaluated over a 6-year period and compared to the predictive validity of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in 95 4-6-year-old children who met full criteria for at least ADHD and 122 demographically-matched nonreferred comparison children. Diagnoses were based on structured assessments of both parents and teachers., Results: All children who met full criteria for HKD also met full DSM-IV criteria for ADHD, but only 26% of ADHD children met criteria for HKD. Children who met criteria for HKD (N = 24), children who would have met criteria for HKD but were excluded from the diagnosis because they concurrently met criteria for an anxiety disorder or depression (N = 16), and the remaining children who met DSM-IV criteria for ADHD (N = 55) all exhibited significantly more symptoms of ADHD and greater social and academic impairment during years 2-7 than nonreferred comparison children. Unlike the two other diagnostic groups, however, children who met strict criteria for HKD were not more likely than comparison children to be injured unintentionally or to be placed in special education., Conclusions: Both ICD-10 HKD and DSM-IV ADHD exhibit predictive validity over 6 years, but ICD-10 HKD appears to under-identify children with persistent ADHD symptoms and related impairment. Children who met criteria for DSM-IV ADHD but not HKD exhibited at least as much functional impairment over time as hyperkinetic children.

Objective: Heavy alcohol drinking is associated with increased prevalence of systemic hypertension (HTN), but the relationship between moderate drinking and HTN remains unclear. We explored the possible role of underreporting among moderate drinkers., Method: In a cross-sectional analysis of 105,378 persons, we defined a subset among persons reporting three or fewer drinks per day that was likely to include a disproportionate number of underreporters. This subset included persons who, on another occasion, indicated intake of three or more drinks per day or who ever had a diagnosis of an alcohol-related condition; these persons are called "positive." Persons who never reported three or more drinks per day and who had no alcohol-related diagnosis were called "negative." Logistic regression models estimated the odds ratios (ORs) for prevalent HTN (140/90 mm Hg or greater) in the positive and negative subgroups, compared with lifelong abstainers as referent. All persons and four race-gender groups were studied, and they were controlled for age, education, smoking, and body mass index. We also studied the relationship of blood liver transaminase enzyme levels in the positive and negative subgroups at specific alcohol intake strata., Results: For persons reporting one to two drinks per day, the OR (95% confidence interval) of HTN was 1.32 (1.21-1.43) for positive persons and 1.16 (1.09-1.25) for negative persons. For those reporting less than one drink per day, the ORs were 0.97 (0.89-1.06) for positives and 0.92 (0.87-0.98) for negatives. For those reporting one to two drinks per day, positive/negative comparisons showed approximately a 75% increased prevalence of high liver transaminase enzymes. For those reporting less than one drink per day, the positive/negative difference was approximately 30%., Conclusion: In these data, increased prevalence of HTN among persons reporting one to two drinks per day appears to be partially due to underreporting of alcohol intake.

The Academic and Behavioral Competencies (ABC) Program, a schoolwide program to reduce classroom disruption and encourage rule following, academic task completion, and homework completion, is described. The program was initially developed and implemented in an elementary school with a high-risk population. Data from teachers, parents, and children indicate high levels of satisfaction with the program. In addition, unobtrusive measures of program impact, reported as reductions in referrals to the principal's office, suspensions, and increases in homework completion rates relative to the year prior to implementation of the program, suggest a preliminary positive impact of the program. A replication is reported for another school district, with teacher evaluations of satisfaction and effectiveness reported, supporting the flexibility and adaptability of the program. Although the present article does not constitute a systematic evaluation of the ABC Program, it presents preliminary data on the process of implementation and stakeholder satisfaction.

The sparseness of prospective data about hemorrhagic stroke (HS) risk among Asian American ethnic groups led to the investigation of 128,934 persons with self-classified ethnicity at health examinations in 1978-1985. Subsequently, 431 persons were hospitalized for HS; 31% for subarachnoid hemorrhage (SAH) and 69% for intracerebral hemorrhage (ICH). Ethnic predictors of HS were studied by Cox proportional hazard models with 7 covariates. With whites as reference, the adjusted relative risk (95% CI) of all Asians for HS was 1.6 (1.1-2.3, p = 0.01), due substantially to increased risks of SAH in Japanese people and ICH in Filipinos. These data mandate emphasis upon preventive measures in these groups.

Objective: Predictive validity is a fundamental consideration in evaluating the DSM-IV diagnostic criteria for attention deficit hyperactivity disorder (ADHD), particularly for younger children., Method: The authors conducted four annual assessments of ADHD and functional impairment using multiple informants in 255 probands and matched comparison children who were 4-6 years old in wave 1., Results: Nearly all children who met full criteria for ADHD in wave 1 met full criteria for ADHD over the next 3 years and continued to display marked functional impairment relative to comparison children, even when intelligence, co-occurring psychopathology, and demographic characteristics were controlled., Conclusions: These findings support the validity of the DSM-IV diagnosis of ADHD in younger children by demonstrating that the symptoms and associated impairment are likely to persist well into elementary school.

We recently reported that a considerable amount of the sodium-d-glucose cotransporter SGLT1 present in Caco-2 cells, a model for human enterocytes, is located in intracellular compartments attached to microtubules. A similar distribution pattern was also observed in enterocytes in thin sections from human jejunum, highlighting the validity of the Caco-2 cell model. Fluorescent surface labeling of live Caco-2 cells revealed that the intracellular compartments containing SGLT1 were accessible by endocytosis. To elucidate the role of endosomal SGLT1 in the regulation of sodium-dependent d-glucose uptake into enterocytes, we compared SGLT1-mediated D-glucose uptake into Caco-2 cells with the subcellular distribution of SGLT1 after challenging the cells with different stimuli. Incubation (90 min) of Caco-2 cells with mastoparan (50 microM), a drug that enhances apical endocytosis, shifted a large amount of SGLT1 from the apical membrane to intracellular sites and significantly reduced sodium-dependent alpha-[(14)C]methyl-D-glucose uptake (-60%). We also investigated the effect of altered extracellular D-glucose levels. Cells preincubated (1 h) with d-glucose-free medium exhibited significantly higher sodium-dependent alpha-[(14)C]methyl-D-glucose uptake (+45%) than did cells preincubated with high d-glucose medium (100 mM, 1 h). Interestingly, regulation of SGLT1-mediated d-glucose uptake into Caco-2 cells by extracellular D-glucose levels occurred without redistribution of cellular SGLT1. These data suggest that, pharmacologically, d-glucose uptake can be regulated by a shift of SGLT1 between the plasma membrane and the endosomal pool; however, regulation by the physiological substrate d-glucose can be explained only by an alternative mechanism.