PubMed Health⌕ Search

Biomedical subjects

Brian Chung

Publications and source records attributed to Brian Chung.

8 recordsLinked to original sources

Febrile seizures in southern Chinese children: incidence and recurrence.

This study investigates the incidence, recurrence, and risk factors of febrile seizures in southern Chinese children. A retrospective study of a 5-year period (March 1998 through February 2003) was conducted for all children admitted with first febrile seizure to a university teaching hospital of Hong Kong, serving a population of 31,700 under 6 years. A total of 565 Chinese children (329 males, 236 females) were identified with mean age of 2.1 +/- 1.1 years. The annual incidence was 0.35%. Among them 16% (91/565) had complex febrile seizures. Family history of febrile and afebrile seizures was present in 17.5% and 2.7% respectively. The mean follow-up period was 2.33 +/- 1.69 years. Altogether 103 children (18%) had recurrence, and the cumulative rates by 1, 2, and 3 years were 12.7%, 18.7%, and 20.5% respectively. Three significant factors were identified for higher risk of recurrence: early age of onset, family history of febrile seizure, and complex febrile seizure. The incidence of first febrile seizure in Chinese children is low compared with the Western world and relatively similar to mainland China. Recurrence is also lower despite similarities in the predictive factors. Further epidemiologic and genetic studies will be necessary to confirm and explain this interethnic variation.

Asian People↗

Self-assembling protein hydrogels with modular integrin binding domains.

Hydrogels with integrin binding activity were created from associating proteins with embedded RGD sequences. These proteins are a modified AC(10)Bcys triblock design composed of acidic A and basic B leucine zipper associating domains flanking a new soluble disordered coil block that contains nine repeats of AGAGAGPEG and three copies of the RGD integrin binding sequence. As with the original AC(10)Bcys design without the embedded RGD sequences, these proteins self-assemble into stable hydrogels at concentrations above approximately 50 mg/mL in a range of solution pH and temperature conditions. The mechanism for hydrogel assembly is the intermolecular association of A and B helical domains into bundles which act as cross-links connected by the soluble central disordered coil domains. The secondary structure of the proteins and the mechanical properties of the hydrogels they form are not adversely affected by the presence of the RGD sequences. The RGD sequences embedded in the disordered coil region support the adhesion, spreading, and polarization of human fibroblast cells on protein coated surfaces. Confocal microscopy studies demonstrated the presence of focal adhesion complexes and organized actin stress fibers in these cells. In contrast, fibroblasts seeded onto surfaces coated with the original AC(10)Bcys protein remained rounded and did not form focal adhesions, indicating that bioactivity is conferred by the presence of the embedded RGD sequences. Such hydrogel-forming bioactive proteins have potential for cell and tissue culture applications.

Amino Acid Sequence↗

Signaling lymphocytic activation molecule-associated protein controls NKT cell functions.

X-linked lymphoproliferative disease (XLP) is a fatal immunological disorder that typically manifests following EBV infection. XLP patients exhibit a number of immune defects including abnormal T, B, and NK lymphocyte function. These defects have been attributed to mutations of Src homology 2 domain-containing gene 1A (SH2D1A), the gene encoding signaling lymphocytic activation molecule-associated protein (SAP), an intracellular adaptor molecule expressed in lymphocytes. We have observed that SAP knockout (SAPKO) mice and humans with XLP have a complete lack of CD1d-restricted NKT cells. As expected, SAPKO mice injected with the NKT cell agonist, alpha-galactosylceramide failed to generate NKT cell IFN-gamma or IL-4. Furthermore, in contrast to wild-type littermates, SAPKO mice coinjected with OVA and alpha-galactosylceramide failed to mount OVA-specific CTL responses. These data suggest that an absence of NKT cells may underlie part of the immune dysregulation seen in SAPKO mice and in XLP patients.

Animals↗

Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule.

Megalin, a member of the low density lipoprotein receptor gene family, is required for efficient protein absorption in the proximal tubule. Recent studies have shown that the low density lipoprotein receptor-related protein, another member of this gene family, is proteolytically processed by gamma-secretase implying a role for low density lipoprotein receptor-related protein in a Notchlike signaling pathway. This pathway has been shown to involve: 1) metalloprotease-mediated ectodomain shedding and gamma-secretase-mediated intramembrane proteolysis of some receptors. Experiments were performed to determine whether megalin undergoes similar processing. By immunocytochemistry, immunoblotting, and a fluorogenic enzyme assay presenilin-1 (required for gamma-secretase activity) and gamma-secretase activity were found in the brush border of proximal kidney tubules where megalin is localized. Using a fluorogenic peptide containing an amyloid precursor protein gamma-secretase cleavage site and Compound E, a specific gamma-secretase inhibitor, we found high levels of gamma-secretase activity in renal brush border membrane vesicles. Immunoblotting analysis of renal microsomes and opossum kidney proximal tubule (OKP) cells using antibodies directed to the cytosolic domain of megalin showed a 35-40-kDa, membrane-associated, carboxyl-terminal fragment of megalin (MCTF). When cells were incubated with 200 nm phorbol 12-myristate 13-acetate, the appearance of the MCTF increased 2.5-fold and was blocked by metalloprotease inhibitors. When the cells were incubated with gamma-secretase inhibitor Compound E, it caused a 2-fold increase in MCTF. Finally, incubating the cells with 1 microm vitamin D-binding protein resulted in a 25% increase in the appearance of the MCTF. In summary, the MCTF is produced by protein kinase C regulated, metalloprotease-mediated ectodomain shedding and is the substrate for gamma-secretase. We postulate that the enzymatic processing of megalin represents part of a novel ligand-dependent signaling pathway in the proximal tubule that links receptor-mediated endocytosis with cell signaling.

Amyloid Precursor Protein Secretases↗

Cerebral palsy: correlation of risk factors and functional performance using the Functional Independence Measure for Children (WeeFIM).

We studied the risk factors affecting the functional status of cerebral palsy. A cross-sectional study of 73 children with cerebral palsy was conducted with the Functional Independence Measure for Children (WeeFIM), which assesses functional skills in the domains of self-care, mobility, and cognition. The mean total Functional Independence Measure for Children quotient was 67.5%. The mean subquotients for self-care, mobility, and cognition were 68.3%, 62.7%, and 69.4%, respectively. The risk factors related to the degree of functional dependency were (1) mental retardation (P = .030), (2) epilepsy (P = .005), (3) type of cerebral palsy (P < .001), and (4) severity of cerebral palsy using the Gross Motor Function Classification System (P < .001) (using univariate analysis). However, when using multivariate analysis, only epilepsy (P = .02) and severity status according to the Gross Motor Function Classification System (P < .001) were significantly related. When the etiology was analyzed, only prematurity was significantly associated with better Functional Independence Measure for Children scores using both univariate (P = .022) and multivariate (P = .007) analyses. The functional status of children with cerebral palsy depends on the severity and the presence of epilepsy. Despite impairment, we found that most children with cerebral palsy could achieve functional independence.

Activities of Daily Living↗

A modified screening tool for autism (Checklist for Autism in Toddlers [CHAT-23]) for Chinese children.

BACKGROUND: There is a recent trend of a worldwide increase in the incidence of autistic spectrum disorder. Early identification and intervention have proved to be beneficial. The original version of the Checklist for Autism in Toddlers (CHAT) was a simple screening tool for identification of autistic children at 18 months of age in the United Kingdom. Children with an absence of joint attention (including protodeclarative pointing and gaze monitoring) and pretend play at 18 months were at high risk of autism. Section A of the CHAT was a self-administered questionnaire for parents, with 9 yes/no questions addressing the following areas of child development: rough and tumble play, social interest, motor development, social play, pretend play, protoimperative pointing (pointing to ask for something), protodeclarative pointing, functional play, and showing. Section B of the CHAT consisted of 5 items, which were recorded with observation of the children by general practitioners or health visitors. The 5 items addressed the child's eye contact, ability to follow a point (gaze monitoring), pretend (pretend play), produce a point (protodeclarative pointing), and make a tower of blocks. A 6-year follow-up study of >16,000 children screened with the CHAT at 18 months in the United Kingdom showed a sensitivity of only 0.40 and a specificity of 0.98, with a positive predictive value (PPV) of 0.26. Rescreening using the same instrument at 19 months for those who failed the 18-month screening yielded a higher PPV of 0.75. Therefore, children were likely to have autism if they failed the CHAT at 18 months and failed again at 19 months. It was estimated that consistent failure in 3 key questions (ie, protodeclarative pointing, gaze monitoring, and pretend play) at 18 months indicated an 83.3% risk of having autism. Because of the poor sensitivity of the original CHAT for autism, a Modified Checklist for Autism in Toddlers (M-CHAT), consisting of 23 questions, with 9 questions from the original CHAT and an additional 14 questions addressing core symptoms present among young autistic children, was designed in the United States. The original observational part (ie, section B) was omitted. The M-CHAT was designed as a simple, self-administered, parental questionnaire for use during regular pediatric visits. The more questions children failed, the higher their risk of having autism. Two criteria were used to measure the sensitivity and specificity of M-CHAT. Criterion 1 used any 3 of the 23 questions, and criterion 2 used 2 of the 6 best questions that could be used to discriminate autism from other groups. The sensitivity and specificity for criterion 1 were 0.97 and 0.95 and those for criterion 2 were 0.95 and 0.99, respectively. M-CHAT had a better sensitivity than the original CHAT, because children up to 24 months of age were screened, with the aim of identifying those who might regress between 18 and 24 months. The 6 best questions of the M-CHAT addressed areas of social relatedness (interest in other children and imitation), joint attention (protodeclarative pointing and gaze monitoring), bringing objects to show parents, and responses to calling. Joint attention was addressed in the original CHAT, whereas the other areas were addressed only in the M-CHAT. To date, there has been no study of the application of either the original CHAT or the M-CHAT for Chinese populations. OBJECTIVES: CHAT-23 is a new checklist translated into Chinese, combining the M-CHAT (23 questions) with graded scores and section B (observational section) of the CHAT. We aimed to determine whether CHAT-23 could discriminate autism at mental ages of 18 to 24 months for Chinese children and to determine the best combination of questions to identify autism. METHODS: A cross-sectional cohort study was performed with 212 children with mental ages of 18 to 24 months. The children were categorized into 2 groups, ie, group 1 (N = 87) (autistic disorder: N = 53; pervasive developmental disorder: N = 33) and group 2 (N = 125) (nonautistic). The checklist included self-ad25) (nonautistic). The checklist included self-administered questionnaires with 23 questions (part A) and direct observations of 5 items by trained investigators (part B). We performed discriminant function analysis to We found that 7 key questions, addressing areas of joint attention, pretend play, social relatedness, and social referencing, were identified as discriminative for autism. For part A, failing any 2 of 7 key questions, ie, question 13 (does your child imitate you? [eg, you make a face; will your child imitate it?]), question 5 (does your child ever pretend, for example, to talk on the phone or take care of dolls, or pretend other things?), question 7 (does your child ever use his/her index finger to point, to indicate interest in something?), question 23 (does your child look at your face to check your reaction when faced with something unfamiliar?), question 9 (does your child ever bring objects over to you [parent] to show you something?), question 15 (if you point at a toy across the room, does your child look at it?), and question 2 (does your child take an interest in other children?), yielded sensitivity of 0.931 and specificity of 0.768. Failing any 6 of all 23 questions produced sensitivity of 0.839 and specificity of 0.848. For part B, failing any 2 of 4 items produced sensitivity of 0.736, specificity of 0.912, and PPV of 0.853. The 4 observational items were as follows: item B1: during the appointment, has the child made eye contact with you? item B2: does the child look across to see what you are pointing at? item B3: does the child pretend to pour out tea, drink it, etc?; item B4: does the child point with his/her index finger at the light? CONCLUSION: We found that integrating the screening questions of the M-CHAT (from the United States) and observational section B of the original CHAT (from the United Kingdom) yielded high sensitivity and specificity in discriminating autism at 18 to 24 months of age for our Chinese cohort. This new screening instrument (CHAT-23) is simple to administer. We found that a 2-stage screening program for autism can offer a cost-effective method for early detection of autism at 18 to 24 months. For CHAT-23, use of both the parental questionnaire and direct observation and use of the criterion of failing any 2 of 7 key questions yielded the highest sensitivity but a relatively lower specificity, whereas use of part B yielded the highest specificity but a lower sensitivity. We recommend identifying the possible positive cases with part A (parental questionnaire) and then proceeding to part B (observation) with trained assessors. The proposed algorithm for screening for autism is as follows. 1) The parents or chief caretakers complete a 23-item questionnaire when their children are 18 to 24 months of age. 2) The parents mail, fax, or hand this 23-item questionnaire to the local child health agency. 3) Clerical staff members check for and score failure, with the criteria of failing any 2 of 7 key questions or failing any 6 of 23 questions; if either criterion is met, then the staff members highlight the medical records of the suspicious cases. 4) Trained child health care professionals observe the children who failed any 2 of 7 key questions or any 6 of 23 questions. These identified patients are observed for 5 minutes for part B of the CHAT-23. 5) Any child who fails any 2 of 4 items requires direct referral to a comprehensive autism evaluation team, for early diagnostic evaluation and early intervention. The high sensitivity and specificity of the criteria observed in our study suggested that CHAT-23 might be used to differentiate children with autism. Additional international collaboration with the use of the CHAT, M-CHAT, and CHAT-23 could provide more prospective epidemiologic data, to establish whether there is a genuine increase in the worldwide incidence of autism.

Attention↗

Pediatric stroke among Hong Kong Chinese subjects.

BACKGROUND: The incidence of pediatric stroke was estimated to be 2.5 to 2.7 cases per 100,000 children per year in North America and 13 cases per 100,000 children per year in France. Stroke is among the top 10 causes of death among children in the United States, with the highest incidence in the first 1 year of life. The annual mortality rate was 0.34 deaths per 100,000 person-years, with an average of 244 deaths per year. Interethnic differences have been demonstrated to be important in pediatric stroke. However, most population-based studies on pediatric stroke were from Europe or North America, and there was a lack of data on the incidence of stroke among Chinese or Asian children. Whether the etiologic patterns and risk factors for death and morbidity among Chinese children with stroke were similar to those described for other ethnic groups was unknown. OBJECTIVES: To calculate the incidence of stroke among Chinese children in Hong Kong and to examine the clinical spectrum, causes, patterns, risk factors, and outcomes of pediatric stroke among Chinese subjects. METHODS: The population of Hong Kong was 6.7 million in 2001, and >98% of our population is Chinese in origin. In Hong Kong, public hospitals under the Hospital Authority provide >95% of the hospital service for the region. We identified children (>1 month to <15 years of age) who were admitted and given a discharge diagnosis of stroke from the Clinical Data Analysis and Reporting System, which is a centralized computerized database for all public hospitals. The discharge coding of stroke used codes from the International Classification of Diseases, 9th Revision, Clinical Modification. Only first admissions during the study period were included. We excluded any subsequent admissions by using multiple demographic characteristics of the patients. The incidence of pediatric stroke was estimated as the number of first hospitalizations divided by the person-years at risk. Since 1991, we had been collecting a database on pediatric stroke (ages of 1 month to 16 years) from a single center (the university-affiliated pediatric unit). The clinical presentation, causes, risk factors, and outcomes for those in the Hong Kong Children's Stroke Registry with follow-up data for > or =2 years were analyzed. Data on outcomes, in terms of survival and neurologic deficits, were studied. For survivors, neurologic deficits were defined as short-term if they resolved within 3 months and long-term if they persisted for >3 months. The severity of deficits was defined as mild when function was minimally affected and the patient remained independent in activities of daily living, moderate when the patient required supervision or partial assistance in activities of daily living or when the deficit caused delay in developmental milestones, and severe when the patient required total or near-total care in activities of daily living. Potential risk factors for death and poor neurologic outcomes, including gender, age at the time of stroke, clinical presentation, causes, and neuroimaging findings, were analyzed. RESULTS: Using projections from census data in 2001, the number of children <15 years of age in Hong Kong from 1998 to 2001 was estimated to be 1,104100 to 1,158800, resulting in 4,545300 person-years. During the same period, 94 children with discharge coding of stroke were identified. Therefore, the estimated incidence of pediatric stroke between 1998 and 2001 was 2.1 cases per 100,000 children-years. The average number of new cases treated annually was 4.5 (0-15 cases/year). Fifty children (28 boys and 22 girls; male/female ratio: 1.27:1) were identified in the 11-year period. The mean age at presentation was 5.6 +/- 4.9 years. Thirty-six strokes (72%) were ischemic and 14 (28%) were hemorrhagic. Despite evaluation for possible underlying causes, 12% (6 cases) remained idiopathic. Eighteen patients with ischemic strokes had cerebral thrombosis, whereas 15 had cerebral embolism. We did not observe any case of sinovenous thrombosis. The 36 cases of ischemic stroke were subtyped according to vascular territories. Eleven cases had infarction involving the middle cerebral artery territory; 2 were limited to the cortical region, 3 were limited to subcortical structures such as the basal ganglia or internal capsule or both, and 6 had complete middle cerebral artery involvement, with cortical and subcortical stroke. Involvement of the anterior cerebral artery occurred in 2 cases, with involvement of cerebellar/basilar artery territories in another 2 cases. The remaining 15 cases had multiple sites of infarction. Three patients experienced secondary hemorrhagic transformation after the initial thrombotic event. Of the 14 patients with hemorrhagic strokes, only 1 had subarachnoid hemorrhage. All others had intracerebral bleeding, at single (N = 9) or multiple (N = 4) loci. Important causes included complications related to congenital heart diseases (N = 15, 30%), vascular diseases (N = 13, 26%), and hematologic diseases (N = 14, 28%). Six cases had no determined causes. One case involved mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and constituted the only case with a metabolic cause. For the 7 patients for whom prothrombotic screening was performed, findings were negative. Seizures (52%) and hemiplegia (34%) were the most common presenting features. Other presenting clinical features included headaches (22%), decreased consciousness (30%), visual field defects (12%), dysphasia (10%), and lethargy (8%). Only 1 patient, with moyamoya disease, had a family history of stroke. The median follow-up time was 8.7 years (range: 2-12.4 years). Nine patients (18%) died, 5 with ischemic stroke and 4 with hemorrhagic stroke. Among the 5 cases of death with ischemic stroke, 3 involved hemorrhagic transformation before death. Seven patients (77%) died within 31 days (range: 2-31 days), whereas the other 2 died 6 months and 2.5 years after the episode. Recurrence occurred in 5 cases (10%). Long-term neurologic deficits occurred among 41% of survivors, including mental retardation (N = 11), epilepsy (N = 7), and hemiplegia (N = 10). The functional deficits were classified as severe in 7 cases, moderate in 3 cases, and mild in 7 cases, for patients with long-term neurologic deficits. Decreased levels of consciousness, hematologic causes, and hemorrhagic transformation (applicable only in ischemic stroke) were significant risk factors associated with high mortality rates. For the 41 patients who survived, the only significant risk factor for long-term neurologic deficits was seizures at the initial presentation. Other factors, such as gender, age, other clinical features, stroke type, vascular territory, other causes, and recurrence of stroke, were all insignificant for both death and long-term deficits. The 3 risk factors identified for death were analyzed in multivariate logistic regression analyses, with adjustment for the confounding variables, and only decreased levels of consciousness remained significant (odds ratio = 15.6). CONCLUSIONS: The incidence of stroke among Chinese children was slightly lower than that in Europe or North America. The etiologic pattern was different in our cohort, and there was no sickle cell anemia, thrombophilia, or sinovenous thrombosis. Despite these differences, however, mortality and long-term neurologic deficit rates were similar.

Adolescent↗

Prevalence of neuromuscular diseases in Chinese children: a study in southern China.

Our objective was to study the prevalence of neuromuscular diseases in Chinese children. A prospective study of neuromuscular diseases in Chinese children was conducted from 1985 to 2001 in Hong Kong, which is a city in southern China. The population census of June 30, 2001, was used to calculate the prevalence of neuromuscular diseases in Chinese children. Altogether, 332 children aged < 19 years at first assessment with neuromuscular diseases confirmed by using electromyography, muscle biopsy, and/or molecular genetic study were included in the study. Of these, 228 (68%) had inherited and 104 (32%) had noninherited neuromuscular diseases. Of the inherited neuromuscular diseases, the most common were the dystrophinopathies, including Duchenne muscular dystrophy (n = 66) and Becker muscular dystrophy (n = 8). Spinal muscular atrophy was the second most common (n = 61). Of the noninherited neuromuscular disorders, myasthenia gravis was the most common (n = 62, 60%). Nearly 88% of the cases of myasthenia gravis were ocular type. The prevalence rate of neuromuscular diseases in June 2001 (n = 291 surviving) is estimated to be 214 x 10(-6). The estimated prevalence rate of neuromuscular diseases in our Chinese children is 1 in 4669.

Adolescent↗