Oral, dental, and craniofacial features in chronic acid sphingomyelinase deficiency.

The aim of this study was to evaluate the oral, dental, and craniofacial features of individuals affected by the chronic forms of acid sphingomyelinase deficiency (ASMD). This study comprised a sample of adult and pediatric patients (n = 8) with chronic ASMD. The individuals underwent oral examinations to evaluate the occurrence of caries, as well as full-mouth periodontal examinations, to assess the occurrence and severity of periodontal diseases. Panoramic and profile radiographs were obtained to analyze dental conditions and craniofacial parameters. Participants also answered questionnaires to identify systemic impairment, parafunctional habits, and bruxism. Dental anomalies of size, shape, and number were found, with agenesis and microdontia being the predominant findings. The average of caries experience was 11.75 (±8.1). Only one patient had periodontal health and all adult individuals had periodontitis at different stages and degrees. Bruxism was found in 87.5% of the sample. The convex profile and maxillary and mandibular retrusion were the most relevant findings in the cephalometric analysis. It is concluded that individuals with chronic ASMD, in addition to several systemic manifestations, present significant modifications in their oral health, from a greater occurrence of dental anomalies, caries, periodontal disease, in addition to skeletal changes.

A multi-intervention protocol to improve sleep quality in a coronary care unit.

AIMS: Poor sleep is a frequent occurrence in the critical illness. Evaluate sleep quality and test the effect of a multi-intervention sleep care protocol in improving sleep quality in a coronary care unit (CCU). METHODS AND RESULTS: Quasi-experimental study, carried out in two phases. During the first phase, the control group (n = 58 patients) received usual care. Baseline sleep data were collected through the Richards-Campbell Sleep Questionnaire (RCSQ) and the Sleep in the Intensive Care Unit Questionnaire (SICUQ). During the second phase (n = 55 patients), a sleep care protocol was implemented. Interventions included actions to promote analgesia, reduce noise, brightness, and other general measures. Sleep data were collected again to assess the impact of these interventions. The intervention group had better scores in overall sleep depth [median (interquartile range)] [81 (65-96.7) vs. 69.7 (50-90); P = 0.046]; sleep fragmentation [90 (65-100) vs. 69 (42.2-92.7); P = 0.011]; return to sleep [90 (69.7-100) vs. 71.2 (40.7-96.5); P = 0.007]; sleep quality [85 (65-100) vs. 71.1 (49-98.1); P = 0.026]; and mean RCSQ score [83 (66-94) vs. 66.5 (45.7-87.2); P = 0.002] than the baseline group. The main barriers to sleep were pain [1 (1.0-5.5)], light [1 (1.0-5.0)], and noise [1 (1.0-5.0)]. The most rated sources of sleep-disturbing noise were heart monitor alarm [3 (1.0-5.25)], intravenous pump alarm [1.5 (1.0-5.00)]. and mechanical ventilator alarm [1 (1.0-5.0)]. All were significantly lower in the intervention group than in the baseline group. CONCLUSION: A multi-intervention protocol was feasible and effective in improving different sleep quality parameters and reducing some barriers to sleep in CCU patients.

Sleep abnormalities in untreated patients with mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease that affects an enzyme responsible for the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in several tissues, such as the upper airways (UA), which leads to the development of obstructive sleep apnea (OSA). Our objective was to determine the prevalence of OSA in a group of untreated patients with MPS VI and the association of OSA with clinical and echocardiographic findings. Patients aged 4 years or older with a biochemical diagnosis of MPS VI were included. Data about clinical history, physical examination, Doppler echocardiogram, and overnight polysomnography (PSG) were collected. Our results showed that of the 28 participants, 14 were boys; mean age was 98.5 months, and mean age at MPS VI diagnosis was 48.4 months. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. PSG results showed that 23:27 patients (85.1%) had OSA which was mild in 4, moderate in 5, and severe in 14 patients. Echocardiograms showed evidence of pulmonary hypertension (PH) in 14 patients. Lower (P = 0.037) and nadir SpO(2) (P = 0.007) were positively associated with PH. Clinical signs suggestive of respiratory abnormalities during sleep were not significantly correlated with the results of PSG. We conclude that the prevalence of OSA in patients with MPS VI was high, and the level of desaturation was positively correlated with PH. Symptoms during sleep were not associated with PSG findings, which suggests that this population should undergo routine PSG as earlier as possible. This study provides baseline data to estimate the potential impact of specific treatments in the sleep abnormalities presented by patients with MPS VI.

Cognitive and behavioral characteristics of children with Williams syndrome: implications for intervention approaches.

Portrayals of individuals with Williams syndrome (WS), a genetic disorder caused by a microdeletion of approximately 25 genes on chromosome 7q11.23, have reached the general public through a variety of media formats. These descriptions are often paradoxical in nature with individuals with WS repeatedly described as demonstrating near-normal language despite the presence of significant intellectual disability and as being extremely sociable and friendly in spite of their seemingly limited understanding of basic social norms. While this depiction of WS served to attract the interest of basic-science researchers, the results of subsequent studies have provided a more nuanced view. For example, rather than across-the-board "near-normal" language, children with WS demonstrate relative strengths in concrete vocabulary and verbal short-term memory, grammatical abilities at the level expected for general intellectual ability, and considerable weakness in relational/conceptual language and pragmatics (social use of language). To provide a more thorough characterization of the WS behavioral phenotype, we summarize recent findings related to intellectual ability, language development, memory development, executive function development, adaptive behavior skills, and behavior as it relates to learning by children with WS. Finally, we briefly discuss intervention approaches that may help children with WS to achieve their full potential.

Sensory modulation impairments in children with Williams syndrome.

The ability to organize information detected by our senses ("sensory modulation") allows us to act or respond effectively to situations encountered, facilitating learning, social behavior, and day-to-day functioning. We hypothesized that children with Williams syndrome (WS) would demonstrate symptoms of poor sensory modulation and that these sensory modulation abnormalities contribute to the phenotype. Participants were 78 children with WS aged 4.00-10.95 years. Based on parent ratings on the Short Sensory Profile [SSP; Dunn, 1999], most children were classified as having definite sensory modulation issues. Cluster analysis identified the presence of two clusters varying in level of sensory modulation impairment. Children in the high impairment group demonstrated poorer adaptive functioning, executive functioning, more problem behaviors, and more difficult temperaments than children in the low impairment group.

Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression.

In mucopolysaccharidosis I, deficiency of alpha-L-iduronidase can cause spinal cord compression (SCC) due to storage of glycosaminoglycans (GAGs) within the cervical meninges. As intravenous enzyme replacement therapy (ERT) is not likely to provide enzyme across the blood-brain barrier, standard treatment for this complication is usually surgical, which has a high morbidity and mortality risk. We report on the use of intrathecal (IT) laronidase in a MPS I patient with SCC who refused the surgical treatment. Assessments were performed at baseline, with clinical and biochemical evaluations, 4-extremity somatosensory evoked potentials, 12 min walk test and MRI studies of the CNS. Changes on these parameters were evaluated after 4 IT infusions of laronidase administered monthly via lumbar puncture. To our knowledge, this was the first MPS patient who received IT ERT. No major adverse events were observed. There were no clinically significant changes in serum chemistries. CSF GAG results revealed pretreatment values slightly above normal standards: 13.3 mg/L (NV < 12 mg/L) which after IT laronidase infusions were within normal levels (10.3 mg/L). 12MWT presented a 14% improvement, with better performance on stability and gait control. Maximum voluntary ventilation showed 55.6% improvement considering the percentage of predicted (26.7% at baseline compared to 41.9%); Maximum Inspiration Pressure improved 36.6% of predicted (26.8% at baseline to 36.7%); Pulmonary diffusion improved 17.6% of predicted %. In conclusion, although the improvement observed in this case with IT laronidase should be confirmed in further patients, this procedure seems to be a safe treatment for SCC in MPS I.

Vocabulary abilities of children with Williams syndrome: strengths, weaknesses, and relation to visuospatial construction ability.

PURPOSE: This project was designed to identify relative strengths and weaknesses in vocabulary ability for children with Williams syndrome (WS) and to demonstrate the importance of stringent matching criteria for cross-group comparisons. METHOD: Children with WS and typically developing (TD) children completed standardized assessments of intellectual and language ability. Children with WS also completed a visuospatial construction ability assessment. RESULTS: Study 1: Concrete and relational vocabulary standard scores were significantly lower for 5- to 7-year-olds with WS than for TD children. Children with WS earned significantly higher standard scores for concrete than for relational vocabulary. When groups were stringently matched for relational vocabulary size, children with WS did not evidence a specific weakness in spatial vocabulary. Study 2: Standard scores for relational vocabulary were similar to those for visuospatial construction ability for 5- to 7-year-olds with WS. Study 3: Nine- to 11-year-olds with WS demonstrated very limited relational vocabulary ability; relational vocabulary ability at 5-7 years was highly correlated with later relational language ability. CONCLUSIONS: Concrete vocabulary is a relative strength for children with WS; relational vocabulary ability is very limited and is at about the level of visuospatial construction ability. Accurate determination of group comparison results depends on stringent group matching.

Transbronchoscopic pulmonary emphysema treatment: 1-month to 24-month endoscopic follow-up.

OBJECTIVE: Describe the results of a 1- to 24-month follow-up of individuals undergoing transbronchoscopic placement of one-way valves. DESIGN: Longitudinal, noncomparative study. SETTING: University hospital. PATIENTS: Nineteen heterogeneous emphysema patients. MEASUREMENTS AND RESULTS: Pulmonary function testing, imaging examination, and videobronchoscopy were performed at 1, 3, 6, 12, and 24 months after the insertion of one-way valves. Mean age was 67.63 +/- 8.71 years, mean body mass index (BMI) was 24.02 +/- 2.65, and mean exposure to smoking was 65.32 +/- 27.46 pack-years (+/- SD). Baseline BODE index (BMI, degree of airflow obstruction and dyspnea, exercise capacity as measured by the 6-min walk test [6MWT]) was 7 to 10 in 10 patients (estimated 4-year mortality, 80%) and 5 to 6 in 9 patients (estimated 4-year mortality, 40%). Sixty-four valves were inserted. There was no procedure-related mortality. Nonsustained atelectasis was observed within 48 h in 2 of 12 patients with right upper lobe occlusion. Fifty-six bronchoscopic examinations were performed in 24 months. Granulomas not requiring treatment were the main complication. Mucus clogging the valve, mainly at 1 month, was easily cleaned. Eighteen patients completed the 1- and 3-month follow-ups, 14 patients completed the 6-month follow-up, 11 patients completed the 12-month follow-up, and 5 patients completed the 24-month follow-up. Improvement was observed in the 6MWT after 1 month (p = 0.028) and in the BODE index at 3 months (p = 0.002). FEV1 or FVC improvement > or = 12% or > or = 150 mL was observed, respectively, in 4 of 18 patients and 8 of 18 patients at 1 month, 4 of 18 patients and 7 of 18 patients at 3 months, and in 3 of 14 patients and 5 of 14 patients at 6 months. After 24 months, one of five patients and three of five patients, respectively, retained an FEV1 and FVC change > or = 12% or > or = 150 mL. Significant improvement (decrease > or = 4%) in the St. George Respiratory Questionnaire was observed at 3 months and 6 months in three of four domains. CONCLUSION: Endobronchial valves are safe, but the criteria to measure improvement and to select patients should be refined. Atelectasis should be reconsidered as primary treatment goal.

Longitudinal assessment of intellectual abilities of children with Williams syndrome: multilevel modeling of performance on the Kaufman Brief Intelligence Test-Second Edition.

Multilevel modeling was used to address the longitudinal stability of standard scores (SSs) measuring intellectual ability for children with Williams syndrome (WS). Participants were 40 children with genetically confirmed WS who completed the Kaufman Brief Intelligence Test-Second Edition (KBIT-2; A. S. Kaufman & N. L. Kaufman, 2004 ) 4-7 times over a mean of 5.06 years. Mean age at first assessment was 7.44 years (range  =  4.00-13.97 years). On average, KBIT-2 Composite IQ, Verbal SS, and Nonverbal SS were stable from 4 to 17 years, although there were significant individual differences in intercept (Composite IQ, Verbal SS, Nonverbal SS) and slope (Composite IQ, Nonverbal SS). Maternal education was significantly related to Verbal SS intercept. No significant sex differences were found. Implications for studies of genotype/phenotype correlations in WS are discussed.

Factor structure of the Children's Behavior Questionnaire in children with Williams syndrome.

To examine the factor structure of temperament in 5-10-year-olds with Williams syndrome, an exploratory factor analysis was conducted on the responses of parents of 192 children on the children's behavior questionnaire. Four factors were identified. Two corresponded to factors reported for typically developing children: effortful control and extraversion/surgency and two corresponded to the temperament constructs of withdrawal/inhibition and irritability/frustration and activity, observed in typically developing infants. Parents of 109 of the 192 participants also completed the anxiety disorders interview schedule, parent version. Children with an anxiety disorder other than specific phobia differed significantly from children without an anxiety disorder on all factors except extraversion/surgency. Children with attention deficit hyperactivity disorder (ADHD) differed significantly from children without ADHD on effortful control and extraversion/surgency.

Pragmatic abilities of children with williams syndrome: a longitudinal examination.

Prior research has indicated that pragmatics is an area of particular weakness for individuals with Williams syndrome (WS). To further address this aspect of the WS social phenotype, we used an individual differences approach to consider both cross-sectional and longitudinal relations among different pragmatic abilities for 14 children with WS, taking into account individual differences in non-verbal reasoning abilities. We also considered the relations between pragmatic abilities and expressive vocabulary ability. Participants were tested at two time points: as 4-year-olds during a 30-min play session with their mothers (Time 1) and an average of 5.87 years later during a one-on-one conversation with a familiar researcher (Time 2). Children's intellectual and expressive vocabulary abilities were assessed at both time points. Results indicated that the ability to verbally contribute information beyond what was required in response to a question (ExtendQ) was significantly related to the ability to verbally contribute new information in the absence of a question (ExtendS) both at age 4 years and during primary school. At age 4, both the ability to pair verbalizations with eye contact in triadic interactions (secondary intersubjectivity) and expressive vocabulary ability were related to both ExtendQ and ExtendS. Finally, both ExtendQ and the ability to pair verbalizations with eye contact (intersubjectivity) at age 4 years predicted ExtendQ at age 9-12 years. The theoretical implications of our findings and the importance of early pragmatic language intervention for children who have WS are discussed.

Comprehension of the communicative intent behind pointing and gazing gestures by young children with Williams syndrome or Down syndrome.

PURPOSE: In this study, the authors examined the ability of preschoolers with Williams syndrome (WS) or Down syndrome (DS) to infer communicative intent as expressed through gestures (pointing and eye-gaze shift). METHOD: Participants were given a communicative or noncommunicative cue involving pointing or gaze shifting in the context of a hiding game. Each child completed 4 conditions formed by crossing Communicative Style (communicative vs. noncommunicative) and Gesture (point vs. gaze shift). RESULTS: At the group level, children in both groups located the toy significantly more often than expected by chance in the communicative condition but performed at chance in the noncommunicative condition. Children in both groups were more likely to infer communicative intent when pointing rather than gaze shifting was used. Individually, despite significantly lower developmental quotient and language standard scores, significantly more children with DS than with WS successfully used the experimenter's communicative gestures. CONCLUSIONS: At the group level, preschoolers with WS or DS were able to comprehend the communicative intent expressed by pointing and gazing gestures in a tabletop task. Children with DS evidenced significantly stronger pragmatic skills than did children with WS, providing further evidence that children with WS have more difficulty with sociocommunication than expected for chronological age or cognitive/language ability.

Referential communication skills of children with Williams syndrome: understanding when messages are not adequate.

Although children with Williams syndrome have relatively good structural language and concrete vocabulary abilities, they have difficulty with pragmatic aspects of language. To investigate the impact of pragmatic difficulties on listener-role referential communication, we administered a picture placement task designed to measure ability to verbalize message inadequacy to a speaker separated by a barrier. Participants were 57 children with Williams syndrome 6 to 12 years of age. When messages were inadequate, children verbalized that a problem was encountered less than half the time. The likelihood that children would indicate a message was insufficient and that children who verbalized message inadequacy also would effectively communicate the problem varied as a function of type of problem encountered, theory of mind knowledge, receptive vocabulary, and CA.

Pulmonary arterial hypertension and thyroid disease.

Recent studies have suggested an association between pulmonary arterial hypertension (PAH) and thyroid diseases (hypothyroidism and hyperthyroidism). This combination has a good prognosis, because the increase in the pulmonary artery pressure is usually slight and reverses after the treatment of the thyroid disease. Although the exact mechanism involved in the pathogenesis of this combination has not yet been established, it has been hypothesized that thyroid hormones and autoimmunity have a direct influence. Due to the high prevalence of thyroid disease in patients with PAH, thyroid function tests should be considered in the investigation of every patient with PAH. In this review, we describe the prevalence of PAH in patients with thyroid diseases and the prevalence of thyroid disease in patients with PAH, as well as addressing the principal effects that thyroid diseases have on the respiratory system. In addition, we report the treatment effects in patients with these diseases.

A Case Study of Early Development in Williams Syndrome: Implications for Early Intervention.

The aim of this article is to provide an in-depth description of the behavioral phenotype of Williams syndrome in a preschool-aged child. Williams syndrome is a neurodevelopmental, multisystem genetic disorder associated with mental retardation that predisposes individuals to a characteristic pattern of strengths and weaknesses in neuropsychological functioning. While much is known about functioning in adults, very few descriptions of early development are available in the literature. Implications for designing early intervention programs for children with this debilitating disorder are discussed.

Recomendações para o manejo da tromboembolia pulmonar, 2010 / Recommendations for the management of pulmonary thromboembolism, 2010

A tromboembolia pulmonar constitui, juntamente com a trombose venosa profunda, a condição denominada tromboembolismo venoso. Apesar dos avanços, a morbidade e a mortalidade atribuídas a essa doença ainda são elevadas, pois os pacientes apresentam doenças mais complexas, são submetidos a um maior número de procedimentos invasivos e sobrevivem por mais tempo. Embora existam inúmeras diretrizes internacionais disponíveis, optou-se por redigir estas recomendações para sua aplicação na prática médica nacional, embasadas nas melhores evidências na literatura e na opinião do grupo de consultores. Este documento é apenas uma ferramenta para o atendimento dos pacientes, e, embora possa ser aplicado na maioria das situações, o médico deve adaptar as informações a sua realidade local e ao caso específico. O diagnóstico de tromboembolia pulmonar é realizado através da combinação da probabilidade clínica pré-teste (escores) com o resultado dos exames de imagem, sendo atualmente o método de eleição a angiotomografia computadorizada. É fundamental a estratificação do risco de desfecho desfavorável, sendo a instabilidade hemodinâmica o preditor mais importante. Pacientes de baixo risco devem ser tratados com heparina, comumente as de baixo peso molecular. Pacientes de alto risco requerem vigilância intensiva e uso de trombolíticos em alguns casos. A longo prazo, os pacientes devem receber anticoagulantes por no mínimo três meses, sendo sua manutenção decidida pela presença de fatores de risco para a recorrência e a probabilidade de sangramento. A profilaxia é altamente eficaz e deve ser amplamente utilizada, tanto em pacientes clínicos como cirúrgicos, conforme os grupos de risco. Finalmente, são feitas recomendações relacionadas ao diagnóstico, tratamento e prevenção da tromboembolia pulmonar.

Pulmonary thromboembolism and deep vein thrombosis together constitute a condition designated venous thromboembolism. Despite the advances, the morbidity and the mortality attributed to this condition are still high, because the patients present with more complex diseases, are submitted to a greater number of invasive procedures and survive longer. Although there are various international guidelines available, we decided to write these recommendations for their application in medical practice in Brazil. These recommendations are based on the best evidence in the literature and the opinion of the advisory committee. This document is only a tool for use in the management of patients. Although the recommendations it contains can be applied to most situations, physicians should adapt its content depending on their local context and on a case-by-case basis. Pulmonary thromboembolism is diagnosed by evaluating pre-test clinical probability (scores) together with the results of imaging studies, the current method of choice being CT angiography. Stratification of the risk for an unfavorable outcome is fundamental. Hemodynamic instability is the most important predictor. Low-risk patients should be treated with heparin, commonly low-molecular-weight heparins. High-risk patients require intensive monitoring and, in some cases, thrombolytic therapy. In the long term, patients should receive anticoagulants for at least three months. The decision to prolong this treatment is made based on the presence of risk factors for the recurrence of the condition and the probability of bleeding. Prophylaxis is highly effective and should be widely used in clinical and surgical patients alike, according to their risk group. Finally, we include recommendations regarding the prevention, diagnosis and treatment of pulmonary thromboembolism.

Hipertensão arterial pulmonar e doenças da tireoide: [revisão] / Pulmonary arterial hypertension and thyroid disease: [review]

Estudos recentes têm sugerido uma associação entre hipertensão arterial pulmonar (HAP) e tireoidopatias (hipotireoidismo e hipertireoidismo). Esta associação tem um bom prognóstico, porque o aumento na pressão da artéria pulmonar geralmente é leve e reversível com o tratamento da tireoidopatia. O mecanismo exato envolvido na patogênese desta associação não está estabelecido, e a influência direta dos hormônios da tireoide e a autoimunidade são consideradas como hipóteses. Devido à alta prevalência de doenças da tireoide em pacientes com HAP, testes de função tireoidiana devem ser considerados na investigação de todo paciente com HAP. Neste artigo de revisão, descrevemos a prevalência de HAP em pacientes com doenças da tireoide e a prevalência de tireoidopatias em pacientes com HAP, assim como destacamos os principais efeitos das doenças da tireoide no sistema respiratório. A seguir, relatamos os efeitos do tratamento destas patologias.

Recent studies have suggested an association between pulmonary arterial hypertension (PAH) and thyroid diseases (hypothyroidism and hyperthyroidism). This combination has a good prognosis, because the increase in the pulmonary artery pressure is usually slight and reverses after the treatment of the thyroid disease. Although the exact mechanism involved in the pathogenesis of this combination has not yet been established, it has been hypothesized that thyroid hormones and autoimmunity have a direct influence. Due to the high prevalence of thyroid disease in patients with PAH, thyroid function tests should be considered in the investigation of every patient with PAH. In this review, we describe the prevalence of PAH in patients with thyroid diseases and the prevalence of thyroid disease in patients with PAH, as well as addressing the principal effects that thyroid diseases have on the respiratory system. In addition, we report the treatment effects in patients with these diseases.