ABSTRACT
This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.
Subject(s)
DiGeorge Syndrome , Adult , Humans , Clinical Relevance , Consensus , DiGeorge Syndrome/genetics , DiGeorge Syndrome/therapy , Genetic Counseling , Surveys and QuestionnairesABSTRACT
This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.
Subject(s)
DiGeorge Syndrome , Adolescent , Humans , Child , DiGeorge Syndrome/genetics , DiGeorge Syndrome/therapy , Genetic Counseling , Surveys and QuestionnairesABSTRACT
The 22q11.2 deletion syndrome (22q11DS) is associated with impaired cognitive functions and increased risk for schizophrenia spectrum disorders. Speech and language deficits are prominent, with evidence of decline anteceding emergence of psychosis. There is paucity of data examining language function in children with 22q11DS with follow-up assessment of psychosis spectrum (PS) symptoms. We examined the association between early language measures, obtained clinically, and PS status, obtained on average 10.1 years later, in 166 youths with 22q11DS, with repeated language testing in 48. Participants were administered the Preschool Language Scale (receptive/expressive), and/or, for school aged children, the Clinical Evaluation of Language Fundamentals (receptive/expressive), and age appropriate IQ tests. The structured interview for prodromal syndromes (SIPS) assessed PS symptoms. We found that performance on all preschool measures showed age associated decline, and males performed more poorly on core composite (receptive/expressive) and receptive language measures. For language assessment later in childhood, poorer performance was consistently associated with subsequent PS status. Furthermore, steeper age-related decline was seen in the PS group across language measures and marginally for full-scale IQ. These findings suggest that while preschool language testing is useful in characterizing performance decline in individuals with 22q11DS, it does not robustly differentiate those with subsequent PS from those without. However, language testing in the school age population can help identify individuals with 22q11DS who are at risk for psychosis. Such data are needed for elucidating a lifespan trajectory for affected individuals and may help understand pathways to psychosis applicable to the general population.
Subject(s)
DiGeorge Syndrome/physiopathology , Psychotic Disorders/genetics , Verbal Behavior/physiology , Adolescent , Child , Child, Preschool , Chromosome Deletion , Cognition , DiGeorge Syndrome/genetics , Female , Humans , Intelligence Tests , Language , Male , Prodromal Symptoms , Schizophrenia/complications , Speech/physiologyABSTRACT
The 22q11.2 deletion syndrome (22q11.2 DS) places affected individuals at an increased risk for neurodevelopmental/cognitive, behavioral and social-emotional difficulties. Poor cognitive functioning and intellectual disabilities, attention and executive functioning deficits, learning disorders, emotional dysregulation and impairments in social processing are common among individuals with 22q11.2 DS. Identifying risk and protective/resilience factors that can be detected in early life and can predict neurodevelopmental outcomes for people with 22q11.2 DS is of significant clinical relevance and might allow for early detection and intervention. Given the focus of this review, we will discuss the possible contributing factors that influence the neurodevelopmental outcome in 22q1.2 DS, the cognitive phenotype in 22q11.2 DS, the different developmental trajectories across life span, and the implications for clinical practice and management.
Subject(s)
DiGeorge Syndrome/genetics , DiGeorge Syndrome/therapy , Age Factors , Cognition , Female , Humans , Male , PhenotypeABSTRACT
Hypocalcemia has been reported in ~50% of patients 22q11.2DS and calcium regulation is known to play a role in neuronal development and synaptic plasticity. Because calcium ions play a role in neuronal function and development, we hypothesized that hypocalcemia would be associated with adverse effects on full scale IQ index (FSIQ) in patients with 22q11.2DS. A retrospective chart review cataloguing the presence or absence of hypocalcemia in 1073 subjects with a laboratory confirmed chromosome 22q11.2 deletion evaluated at the Children's Hospital of Philadelphia was conducted. 852/1073 patients had an endocrinology evaluation with laboratory confirmed calcium levels. 466/852 (54.7%) had a diagnosis of hypocalcemia. 265/1073 subjects ranging from 0 to 51 years of age had both calcium levels measured and a neuropsychological evaluation yielding a FSIQ. The mean FSIQ for 146/265 patients with hypocalcemia was 77.09 (SD = 13.56) and the mean FSIQ for 119/265 patients with normocalcemia was 77.27 (SD = 14.25). The distribution of patients with intellectual disability (ID) (FSIQ<69), borderline IQ (FSIQ 70-79), and average IQ (FSIQ>80) between the hypocalcemic and normocalcemic groups was not statistically significant (χ2 = 0.2676, p = 0.8748). Neonatal hypocalcemic seizures were not found to be associated with ID. We found no difference in FSIQ between the hypocalcemic and non-hypocalcemic patients with 22q11.2DS. As our findings differ from a previous report in adult subjects, we speculate that this may reflect a potential benefit from early treatment of hypocalcemia and may support early 22q11.2 deletion detection in order to offer prompt diagnosis and subsequent treatment of hypocalcemia.
Subject(s)
Chromosomes, Human, Pair 22/genetics , DiGeorge Syndrome/etiology , Hypocalcemia/psychology , Intelligence Tests , Adolescent , Adult , Calcium/blood , Child , Child, Preschool , Chromosome Deletion , DiGeorge Syndrome/psychology , Female , Humans , Hypocalcemia/etiology , Infant , Infant, Newborn , Intellectual Disability/genetics , Male , Middle Aged , Wechsler ScalesABSTRACT
22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by recurrent, chromosome-specific, low copy repeat (LCR)-mediated copy-number losses of chromosome 22q11. The Children's Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. Most individuals are Caucasian and older than 8 years. The mean age at diagnosis was 3.9 years. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale intelligence quotient was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most individuals, but dermatoglyphic patterns of our cohort are similar to normal controls. This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.
Subject(s)
DiGeorge Syndrome/etiology , Adolescent , Adult , Child , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 22 , Comorbidity , DiGeorge Syndrome/diagnosis , DiGeorge Syndrome/epidemiology , Female , Gastrointestinal Diseases/etiology , Heart Defects, Congenital/etiology , Humans , Longitudinal Studies , Male , Mortality , Philadelphia/epidemiology , Transition to Adult CareABSTRACT
22q11.2 Deletion Syndrome (22q11DS) is a multisystem disorder caused by a hemizygous deletion within 22q11.2. Patients with the deletion display a wide range of cognitive deficits. The gene catechol-O-methyl-transferase (COMT) resides in the typically deleted region of 22q11.2 and is rendered hemizygous in individuals affected by the 22q11DS. COMT is a critical enzyme in the degradation of catecholamine neurotransmitters in the brain. A functional polymorphism, Val158 Met, has been associated with a variety of neurocognitive outcomes. In this study, 159 patients with 22q11DS were analyzed for a potential association between intelligence quotient (IQ) and COMT genotype. We performed a univariate analysis for overall influence and modified our analysis to focus on possible differences between average, borderline, and intellectually impaired patients. No correlation between COMT genotype and IQ performance was found. © 2016 Wiley Periodicals, Inc.
Subject(s)
22q11 Deletion Syndrome/genetics , Catechol O-Methyltransferase/genetics , Catechol O-Methyltransferase/metabolism , 22q11 Deletion Syndrome/metabolism , Adolescent , Child , Chromosome Deletion , Chromosomes, Human, Pair 22 , Cognition , Cognition Disorders/genetics , Female , Genetic Association Studies/methods , Genetic Predisposition to Disease , Hemizygote , Humans , Intelligence Tests , Male , Methionine/genetics , Polymorphism, Single Nucleotide/genetics , Valine/genetics , Young AdultABSTRACT
OBJECTIVE: Transcranial magnetic stimulation (TMS) uses a medical device that applies magnetic pulses noninvasively to the cortex of the brain to depolarize neurons. We tested its safety and efficacy in young persons with a diagnosis of attention-deficit/hyperactivity disorder (ADHD). METHODS: Transcranial magnetic stimulation was applied to the right prefrontal cortex at 10 Hz, at 100% of the observed motor threshold, for 2000 pulses per session, in a 10-session course over 2 weeks in a sham-controlled crossover design (n=9). There was 1 week of no TMS between the active and sham phases. Safety of TMS was assessed by means of serial audiometry, neuropsychological testing, and electroencephalogram (EEG) at baseline, midpoint, and end point of the study. Efficacy was assessed as a primary outcome by changes in the Clinical Global Impression-Improvement (CGI-I) scale and secondarily by change in the ADHD-IV scale. RESULTS: Transcranial magnetic stimulation was found to be safe, with no serious adverse events and no discontinuations due to adverse effects. All randomized subjects completed the full course of sessions. There were no significant changes in auditory thresholds or in electroencephalographic assessments. Neuropsychological testing showed no significant differences between active and sham groups. There was an overall significant improvement in the clinical global impression of improvement and the ADHD-IV scales across the study phases (active and sham TMS combined; P<0.01), but the change between active and sham TMS phases did not differ. CONCLUSION: Transcranial magnetic stimulation was found to be safe, with no serious adverse events observed in this pilot study. Improvement in symptoms was observed across the combined phases of the study, although there was no difference between the active and sham forms of TMS. Effects of clinical importance should be further assessed in larger controlled studies.
Subject(s)
Attention Deficit Disorder with Hyperactivity/therapy , Transcranial Magnetic Stimulation/methods , Adolescent , Attention Deficit Disorder with Hyperactivity/psychology , Audiometry , Cross-Over Studies , Electroencephalography , Endpoint Determination , Female , Humans , Intelligence Tests , Male , Mental Disorders/complications , Neuropsychological Tests , Pilot Projects , Prefrontal Cortex/physiology , Psychiatric Status Rating Scales , Transcranial Magnetic Stimulation/adverse effects , Treatment Outcome , Young AdultABSTRACT
Learning and intellectual disabilities are hallmark features of 22q11.2 deletion syndrome. Data are limited, however, regarding influences on full-scale IQ (FSIQ). Here, we investigated possible 22q11.2 deletion parent-of-origin effects. In 535 individuals, we compared FSIQ (≥50), 481 with de novo and 54 with inherited 22q11.2 deletions. In the subsets with data available, we examined parent-of-origin effects on FSIQ. We used linear regression models to account for covariates. Median FSIQ was significantly higher in de novo vs. inherited deletions (77; range 50−116 vs. 67; range 50−96, p < 0.0001). Results remained significant using a regression model accounting for age at IQ testing, sex and cohort site. No significant parent-of-origin differences in FSIQ were observed for de novo deletions (n = 81, 63.0% maternal; p = 0.6882). However, median FSIQ was significantly lower in maternally than in paternally inherited familial deletions (65, range 50−86 vs. 71.5, range 58−96, respectively, p = 0.0350), with the regression model indicating an ~8 point decrement in FSIQ for this variable (p = 0.0061). FSIQ is higher on average in de novo than in inherited 22q11.2 deletions, regardless of parental origin. However, parent-of-origin appears relevant in inherited deletions. The results have potential clinical implications with further research needed to delineate possible actionable mechanisms.
Subject(s)
DiGeorge Syndrome , Intellectual Disability , Humans , DiGeorge Syndrome/genetics , Chromosome Deletion , Intellectual Disability/genetics , ChromosomesABSTRACT
Intelligence quotient (IQ) testing is standard for evaluating cognitive abilities in genomic studies but requires professional expertise in administration and interpretation, and IQ scores do not translate into insights on implicated brain systems that can link genes to behavior. Individuals with 22q11.2 deletion syndrome (22q11.2DS) often undergo IQ testing to address special needs, but access to testing in resource-limited settings is challenging. The brief Penn Computerized Neurocognitive Battery (CNB) provides measures of cognitive abilities related to brain systems and can screen for cognitive dysfunction. To examine the relation between CNB measures and IQ, we evaluated participants with the 22q11.2DS from Philadelphia and Tel Aviv (N = 117; 52 females; mean age 18.8) who performed both an IQ test and the CNB with a maximum of 5 years between administrations and a subsample (n = 24) who had both IQ and CNB assessments at two time points. We estimated domain-level CNB scores using exploratory factor analysis (including bifactor for overall scores) and related those scores (intraclass correlations (ICCs)) to the IQ scores. We found that the overall CNB accuracy score showed similar correlations between time 1 and time 2 as IQ (0.775 for IQ and 0.721 for CNB accuracy), correlated well with the IQ scores (ICC = 0.565 and 0.593 for time 1 and time 2, respectively), and correlated similarly with adaptive functioning (0.165 and 0.172 for IQ and CNB, respectively). We provide a crosswalk (from linear equating) between standardized CNB and IQ scores. Results suggest that one can substitute the CNB for IQ testing in future genetic studies that aim to probe specific domains of brain-behavior relations beyond IQ.
Subject(s)
Arachnodactyly , DiGeorge Syndrome , Marfan Syndrome , Adolescent , Female , Humans , Intelligence/genetics , Intelligence TestsABSTRACT
Critical feminist approaches to eating disorders and "obesity" have recently come under criticism for relying too heavily on textual- and image-based analyses of health, identity and body weight, shape, and size. In this article, we examine qualitative interviews with self-identified anorexic and "obese" women using a new material feminist lens-particularly the work of Karen Barad-to see what this perspective contributes to conceptualizations of weight-based oppressions. In addition to outlining how the material world actively participates in ongoing processes of oppression, we also highlight how the body presses back, offering up potentially less oppressive processes of materialization. The article concludes on a cautiously optimistic note, pointing to how a new materialist framework may draw attention to micropolitical processes of becoming otherwise.
Subject(s)
Body Image/psychology , Feminism , Obesity/psychology , Thinness/psychology , Anorexia Nervosa/psychology , Female , HumansABSTRACT
RéSUMé: OBJECTIF: L'objectif était d'étudier le déploiement des discours sur la vaccination contre les VPH (VVPH) et leur impact sur les filles, les parents, les infirmiers/infirmières et les médecins canadiens. MéTHODES: Des entrevues ont été réalisées avec des participant(e)s (n = 146) de quatre provinces canadiennes. Une analyse poststructuraliste du discours a permis d'examiner les campagnes de VVPH et les transcriptions d'entrevues pour documenter la façon dont les participant(e)s interprètent les VVPH et se positionnent comme sujets au sein des discours de l'industrie ou des agences de santé publique. RéSULTATS: Les campagnes de VVPH sont sexistes, hétéro-normatives et trompeuses. Émergeant de l'analyse des entrevues est le manque d'information des filles et des parents en ce qui a trait à la VVPH. Les mères se construisent en tant que bio-citoyennes responsables, mais au prix de l'impuissance, de l'anxiété et de la peur ressenties parallèlement à l'impératif d'agir pour minimiser le risque de cancer de leur fille. Quant aux professionnel(le)s de la santé, ils s'approprient les discours dominants sur la VVPH et utilisent la peur comme stratégie pour fabriquer le consentement pour la VVPH. Les occasions de dialogue sur la VVPH et la santé sexuelle des filles sont perdues et les positions en tant que sujets sont problématiques pour tous les types de participant. CONCLUSIONS: Nous nous questionnons à savoir si la santé publique est bien servie quand les discours sur la VVPH transforment des corps en santé en corps « à risque ¼ et quand la peur du cancer est instrumentalisée pour la pharmacologisation de la santé publique.
Subject(s)
Communication , Health Knowledge, Attitudes, Practice , Papillomavirus Vaccines , Professional-Patient Relations , Vaccination/psychology , Adolescent , Canada , Child , Female , Humans , Immunization Programs , Male , Neoplasms/prevention & control , Neoplasms/psychology , Nurses/psychology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Parents/psychology , Physicians/psychology , Public Health , Qualitative Research , Risk Assessment , Young AdultABSTRACT
PURPOSE: To measure the effect of the implantation of a glaucoma drainage device on the intraocular pressure (IOP) during the implantation surgery. METHOD: We implanted telemetry devices into 1 eye each of 3 white New Zealand rabbits. Once the telemetry was found to be working and the rabbits had fully recovered from surgery, we implanted a glaucoma drainage device into the same eye while continually monitoring the IOP with the telemetry devices. RESULTS: During surgery IOP was extremely variable, however, extremely high pressures were recorded in association with suturing and viscoelastic injection. DISCUSSION: The fact that pressures are significantly raised during some surgical events should make surgeons aware that manipulations need to be kept as short as possible to prevent further potential damage to glaucomatous optic nerves. There is a possibility of dramatically raising the IOP during surgery, specifically in complicated cases requiring prolonged manipulation and/or forcible deepening of the anterior chamber. In such cases, it may be a good idea to time the duration of manipulations to prevent prolonged episodes of elevated IOP.
Subject(s)
Glaucoma Drainage Implants , Glaucoma/surgery , Intraocular Pressure/physiology , Prosthesis Implantation , Animals , Female , Glaucoma/physiopathology , Rabbits , Telemetry/instrumentation , Tonometry, Ocular/methodsABSTRACT
PURPOSE: The purpose of this study was to determine the risk of a steroid pressure response from inhaled corticosteroids. PATIENTS AND METHODS: This randomized, double-masked, placebo-controlled trial included 22 adults with well-controlled open-angle glaucoma or ocular hypertension. Consenting participants were randomized to a 6-week course of twice-daily fluticasone propionate 250-µg metered-dose inhaler or saline placebo metered-dose inhaler. Biweekly clinic visits included masked Goldmann applanation tonometry and assessment to identify adverse effects. Primary outcome was mean intraocular pressure (IOP) at week 6. Secondary outcomes included IOP elevation of >20% at 2 consecutive visits, adherence, side effects, and logMAR visual acuity. RESULTS: A total of 10 patients in each arm completed the study. There were no statistically significant differences in IOP between groups at baseline (14.3±3.0 and 15.6±3.6 mm Hg in steroid and placebo groups, respectively, P=0.39) or at week 6 (14.7±2.4 and 14.8±3.8 mm Hg in steroid and placebo groups, respectively, P=0.92). Adherence was >80% for all participants. There were no statistically significant differences between groups in any secondary measures. One patient in the steroid group met the secondary end point of >20% elevation in IOP (IOP increased from baseline of 9 to 11 mm Hg at weeks 2 and 4). CONCLUSIONS: We found no clinically significant increase in mean IOP in patients with well-controlled open-angle glaucoma and ocular hypertension after 6 weeks of twice-daily inhaled fluticasone propionate compared with inhaled placebo. No participants exceeded their individualized target IOP. There were no differences in secondary outcomes.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Fluticasone/administration & dosage , Glaucoma, Open-Angle/drug therapy , Glucocorticoids/administration & dosage , Intraocular Pressure/drug effects , Administration, Inhalation , Adolescent , Adrenal Cortex Hormones , Adult , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Double-Blind Method , Female , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Ocular Hypertension/drug therapy , Tonometry, Ocular , Young AdultABSTRACT
PURPOSE: To assess the validity of a preimplantation flow test to predict early hypotony [intraocular pressure (IOP)≤5 mm Hg on 2 consecutive visits and hypertensive phase (HP) (IOP>21 mm Hg) after Ahmed Glaucoma Valve (AGV) implantation. PATIENTS AND METHODS: Prospective interventional study on patients receiving an AGV. A preimplantation flow test using a gravity-driven reservoir and an open manometer was performed on all AGVs. Opening pressure (OP) and closing pressure (CP) were defined as the pressure at which fluid was seen to flow or stop flowing through the AGV, respectively. OP and CP were measured twice per AGV. Patients were followed for 12 weeks. RESULTS: In total, 20 eyes from 19 patients were enrolled. At 12 weeks the mean IOP decreased from 29.2±9.1 to 16.8±5.2 mm Hg (P<0.01). The mean AGV OP was 17.5±5.4 mm Hg and the mean CP was 6.7±2.3 mm Hg. Early (within 2 wk postoperative) HP occurred in 37% and hypotony in 16% of cases. An 18 mm Hg cutoff for the OP gave a sensitivity of 0.71, specificity of 0.83, positive predictive value of 0.71, and negative predictive value of 0.83 for predicting an early HP. A 7 mm Hg cutoff for the CP yielded a sensitivity of 1.0, specificity of 0.38, positive predictive value of 0.23, and negative predictive value of 1.0 for predicting hypotony. CONCLUSIONS: Preoperative OP and CP may predict early hypotony or HP and may be used as a guide as to which AGV valves to discard before implantation surgery.
Subject(s)
Aqueous Humor/physiology , Diagnostic Techniques, Ophthalmological , Glaucoma Drainage Implants , Glaucoma/surgery , Intraocular Pressure/physiology , Ocular Hypertension/diagnosis , Ocular Hypotension/diagnosis , Aged , False Positive Reactions , Female , Glaucoma/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Prosthesis Implantation , Sensitivity and Specificity , Tonometry, Ocular , Treatment OutcomeABSTRACT
The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.
Subject(s)
Catechol O-Methyltransferase/genetics , Catechol O-Methyltransferase/metabolism , Child Behavior Disorders/genetics , Chromosomes, Human, Pair 22/genetics , DiGeorge Syndrome/enzymology , DiGeorge Syndrome/genetics , Gene Deletion , Genotype , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/etiology , Female , Humans , Male , Polymorphism, Genetic/genetics , Severity of Illness IndexABSTRACT
PURPOSE: To determine the pressure required to prime an Ahmed Glaucoma Valve (AGV) and determine whether the valve can be damaged by "over-priming pressure." METHODS: Three AGVs, a syringe pump, and a manometer were used to assess priming pressure. Balanced salt solution was pumped through the AGV tube at increasing pressures until a jet of fluid was seen to eject from the AGV, as per manufacturer instructions. This was repeated 3 times for 3 different virgin AGVs giving the "priming pressure." A second experiment used the same experimental set up to determine the "over-priming pressure" on 3 other AGVs. Fluid was pumped through the AGV at increasing pressures until evidence of damage was seen. The valve function was assessed before and after the "over-priming" stress test. Valve function was determined by the closing pressure, which is the pressure at which the valve closes and fluid was no longer seen passing through the valve. RESULTS: The priming pressure in the 3 AGVs was 2844, 3154, and 3051 mm Hg (mean, 3017±158 mm Hg). The maximum pressure generated using the syringe pump was 10,860, 10,343, and 10,860 mm Hg (mean, 10,688±299 mm Hg). No damage was observed in the valve mechanism. AGV closing pressure before the "over-priming" stress test was 8, 6, and 13 mm Hg and after the stress test was 6, 7, and 13 mm Hg. CONCLUSION: This study demonstrates that the priming pressure is consistent at around 3000 mm Hg. In addition, over-priming is not likely to damage or disturb the closing pressure.
Subject(s)
Acetates/administration & dosage , Glaucoma Drainage Implants , Minerals/administration & dosage , Pressure , Sodium Chloride/administration & dosage , Catheters , Drug Combinations , Infusion Pumps , ManometryABSTRACT
OBJECTIVE: The 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) is associated with attentional problems and executive dysfunction, and is one of the highest known risk factors for schizophrenia. These behavioral manifestations of 22q11.2 deletion syndrome could result from haploinsufficiency of the catechol O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype as a predictor of prefrontal cognitive function in patients with 22q11.2 deletion syndrome. METHOD: Patients with confirmed 22q11.2 deletions (N=44) underwent neurocognitive testing following Val(158)Met genotyping (Met hemizygous: N=16; Val hemizygous: N=28). RESULTS: Analyses of covariance revealed that Met-hemizygous patients performed significantly better on a composite measure of executive function (comprising set-shifting, verbal fluency, attention, and working memory) than did Val-hemizygous patients. CONCLUSIONS: These data are consistent with those of previous studies in normal individuals, suggesting that a functional genetic polymorphism in the 22q11 region may influence prefrontal cognition in individuals with COMT haploinsufficiency.
Subject(s)
Catechol O-Methyltransferase/genetics , Cognition/physiology , DiGeorge Syndrome/genetics , Polymorphism, Genetic , Prefrontal Cortex/physiology , Alleles , Child , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 22/physiology , DiGeorge Syndrome/enzymology , DiGeorge Syndrome/physiopathology , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Methionine/genetics , Neuropsychological Tests , Prefrontal Cortex/enzymology , Valine/geneticsABSTRACT
The role of echocardiography for the evaluation of thrombus formation on indwelling intracardiac catheters is well established. Considerably less well described, however, are the echocardiographic characteristics of the so-called retained fibrin sheath, a sleeve of fibrin that surrounds the catheter at the point at which it enters the vein that commonly remains adherent to the vessel wall after catheter removal. The authors report the transesophageal echocardiographic findings of a retained fibrin sheath following catheter removal in a patient with end-stage renal disease and infective endocarditis of the aortic valve.
Subject(s)
Aortitis/diagnostic imaging , Aortitis/etiology , Cardiac Catheterization/adverse effects , Echocardiography, Transesophageal/methods , Fibrin/adverse effects , Foreign-Body Reaction/diagnostic imaging , Foreign-Body Reaction/etiology , Female , Humans , Middle Aged , Renal Dialysis/adverse effectsABSTRACT
PURPOSE: To measure closing pressure in a series of new Model FP7 silicone Ahmed Glaucoma Valves (AGVs), using an in vitro gravity-driven system, in which closing pressure was measured directly from a dual manometer/pressure reservoir. METHOD: A straight length of tubing served as an open manometer, which connected via a 3-way stopcock to the inlet of the AGV submerged under 1.5 cm of balanced saline solution (BSS). Six AGV were assessed in 5 sequential trials and the mean inlet pressure at 90 minutes was recorded as the closing pressure. After testing, a single valve was primed a second time using greater force and retested. Control trials were performed with a submerged 26-G cannula opening directly into the BSS bath. RESULTS: At 90 minutes, the 6 valves equilibrated at a mean inlet pressure of 7.1 mm Hg, with a range from 1.4 to 13.5 mm Hg. Closing pressures at or less than 5 mm Hg were measured in half (3/6) of the valves tested. The average flow of BSS across the valves in the final 30 minutes was less than 1.5x10(-2) microL/min. In the single valve reperfused under greater pressure, the closing pressure increased. CONCLUSIONS: Model FP7 AGVs, in vitro, exhibit significant variability in closing pressure, with half closing at intraocular pressures considered potentially problematic in clinical situations. The results of the high-pressure perfusion experiment suggest that more research into the priming process is required so a precise description can be developed for surgeons.