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Biomedical subjects

I Chan

Publications and source records attributed to I Chan.

At least 19 recordsLinked to original sources
PubMed2006

Illness-related factors, stress and coping strategies in relation to psychological distress in HIV-infected persons in Hong Kong.

This study examined the relationships among illness-related factors, stress, coping strategies and psychological distress in HIV-infected persons in Hong Kong (N=118). Multiple regression analyses were used to examine the models of psychological distress as a function of demographic factors, illness-related factors, psychosocial stressors and coping. Results showed that positive thinking was inversely related to psychological distress and avoidance was associated with higher level of anxiety. However, the use of problem solving was found to be inversely related to anxiety. Results are discussed in the context of Chinese culture and the service in Hong Kong.

Adaptation, Psychological↗
PubMed2005

Multiple dermatofibromas associated with lupus profundus.

We report a 58-year-old Afro-Caribbean woman who presented with more than 20 dermatofibromas on the body particularly on the back, arms and legs. These developed spontaneously over the course of 5 years. She also had a long-standing 5 x 2-cm area of lipoatrophy on the right upper arm and a 2-year history of several inflammatory subcutaneous nodules developing on the upper chest and left breast. These were confirmed histologically as lupus profundus. Apart from a mild arthritis, she had no other markers for systemic lupus erythematosus and was systemically well. Multiple dermatofibromas are rare. There are around 30 reports of multiple dermatofibromas associated with systemic diseases. More than half of these cases were associated with systemic lupus erythematosus, with or without systemic steroid therapy and about one-third were associated with HIV infection. Although the mechanism is unknown, it appears that multiple dermatofibromas are associated with autoimmune diseases or altered immune states. This is the first case of multiple dermatofibromas associated with lupus profundus. The knowledge of such associations may contribute to the understanding of the pathogenesis of dermatofibromas, which is as yet unknown.

Autoimmune Diseases↗
PubMed2005

Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer.

Multiple cutaneous and uterine leiomyomas is an autosomal dominant condition that results in benign smooth muscle tumours of the skin and, in females, uterine fibroids. This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer syndrome in which affected individuals may develop the rare type II papillary renal cell cancer, in addition to skin leiomyomas. Recently, heterozygous mutations in the gene encoding fumarate hydratase have been found to underlie both conditions. Fumarate hydratase is an enzyme that catalyses the conversion of fumarate to malate in the Kreb's cycle and may also function as a tumour suppressor gene. We report a family with multiple leiomyomas, uterine fibroids and papillary renal cell cancer. The proband is a 77-year-old Polish woman who developed multiple cutaneous leiomyomas on her right upper arm in her thirties and subsequently underwent a hysterectomy for uterine fibroids in her forties. She has four offspring: her eldest daughter also has skin and uterine leiomyomas with a similar onset; her son has multiple skin leiomyomas and in addition was diagnosed with metastatic papillary renal cell cancer at the age of 50 years; the two youngest daughters are unaffected. DNA sequencing in all the affected individuals disclosed a heterozygous G-->C substitution at nucleotide 173 of the fumarate hydratase gene, that converts an arginine residue (CGA) to proline (CCA). This missense mutation has not been reported previously and is designated R58P. Interestingly, the clinically asymptomatic 20-year-old son of the individual with renal cancer was also found to be heterozygous for R58P. It is likely that he will develop skin leiomyomas in the future but the risk of renal cancer is difficult to predict. Nevertheless, detection of this mutation has important implications for screening and genetic counselling in this and other family members.

Aged↗
PubMed2005

Rapp-Hodgkin syndrome and the tail of p63.

We report the clinical and molecular abnormalities in a 19-year-old woman with Rapp-Hodgkin ectodermal dysplasia syndrome. The physical features include mid-facial hypoplasia, uncombable hair, cleft palate and bifid uvula, lacrimal duct obstruction and dry skin. Sequencing of the p63 gene reveals a new heterozygous frameshift mutation, 1787delG, in exon 14. The frameshift results in changes to the tail of p63 with the addition of 68 missense amino acids downstream and a delayed termination codon that extends the protein length by 21 amino acids. These changes are predicted to disrupt the normal repressive function of the transactivation inhibitory domain leading to gain-of-function for at least two isoforms of the p63 transcription factor. The expanding p63 mutation database demonstrates that there is overlap between Rapp-Hodgkin syndrome and several other ectodermal dysplasia syndromes, notably Hay-Wells syndrome, and that characterization of the functional consequences of these p63 gene mutations at a molecular and cellular level is likely to provide further insight into the clinical spectrum of these developmental malformation syndromes.

Adult↗
PubMed2005

Paediatric out-of-hospital cardiac arrests: epidemiology and outcome.

INTRODUCTION: Little information is available regarding the outcome of children in our local population who sustained pre-hospital cardiac arrest. This study was performed to determine the survival rate among children after out-of-hospital cardiac arrest, to describe the epidemiology, and to identify predictors of survival. METHODS: The records of 85 children who presented to a paediatric emergency department in cardiac arrest, between 1 June 1997 and 31 September 2001, were reviewed. The characteristics of the patients, cardiac arrest circumstances, and the outcomes of arrest were analysed. RESULTS: 85 children presented to the emergency department in cardiac arrest during the 52-month study period. 26 out of 85 children (30.6 percent) with cardiac arrest had return of spontaneous circulation (ROSC) after resuscitation efforts at the emergency department. Only four (4.7 percent) survived to be discharged from hospital and three of them survived beyond one year. Two of the cardiac arrest survivors had no change in the neurological status, with the remaining two sustaining severe neurological deficits. Emergency medical service was activated in only 63.7 percent of the patients. 34 percent of the arrests were witnessed, and only 22.9 percent of the children received bystander cardiopulmonary resuscitation (CPR). The positive predictors for survival to hospital discharge in a bivariate analysis were witnessed arrest (p-value is equal to 0.012), presence of bystander CPR (p-value is equal to 0.003), and duration of resuscitation (p-value is equal to 0.028). None who had more than 30 minutes of resuscitation in the emergency department survived. In a multivariate analysis with a logistic regression model, the only two independent predictors of ROSC were witnessed arrest (odds ratio is 3.049; 95% confidence interval [CI] is 1.101-8.444; p-value is equal to 0.032) and duration of resuscitation (odds ratio is 0.353; 95% CI is 0.146 - 0.854; p-value is equal to 0.021). CONCLUSION: Out-of-hospital cardiac arrest in children has a poor prognosis and prolonged resuscitation at the emergency department beyond 30 minutes does not improve survival.

Adolescent↗
PubMed2004

Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa.

BACKGROUND: Lipoid proteinosis (LiP) is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LiP. Since the early 1970s it has been recognized that South Africa has one of the largest groups of LiP patients worldwide, suggesting a probable founder effect. As LiP patients present with considerable clinical variability, this group of patients offers a unique opportunity for genotype-phenotype correlation. OBJECTIVES: To assess the clinical features and the molecular basis of LiP in patients from the Namaqualand area of the Northern Cape province of South Africa and to examine molecular evidence for a founder effect. SUBJECTS AND METHODS: The LiP patient cohort consisted of 29 Coloured patients from Namaqualand and a further seven Caucasoid patients from other areas of South Africa. The control group included 100 healthy geographically and ethnically matched individuals from Namaqualand. Samples were collected after informed consent and with ethics committee approval from the University of the Witwatersrand. LiP patients were examined clinically and a structured recording sheet was completed. A brief neurological evaluation was also performed. The LiP founder effect was investigated at the molecular level by ECM1 mutation detection and haplotype analysis. RESULTS: The most consistent clinical signs for a diagnosis of LiP in this group were a hoarse voice and thickened sublingual frenulum leading to restricted tongue movement. Homozygosity for a nonsense mutation in exon 7 of the ECM1 gene, Q276X, was identified in all patients (Coloured and Caucasoid). Despite this genetic homogeneity, considerable clinical variability in skin presentation and psychiatric involvement was observed. Haplotype analysis using markers from a 9.98-Mb region around the ECM1 locus confirmed the founder effect with a founder core haplotype, 19-Q276X-12 (ND1-ECM1-D1S2343), in all but four LiP-associated alleles (n = 58). A LiP carrier rate of 1 in 9 was observed among the 100 Namaqualand controls, predicting a LiP incidence of 1 in 324 in this community. CONCLUSIONS: Although several consistent clinical features in LiP patients homozygous for the Q276X mutation in the ECM1 gene were observed, there remains considerable clinical variability. This suggests the action of genetic and environmental modifiers of disease severity. Strong molecular evidence supports a single founder effect for the high prevalence of LiP in South Africans, both Coloured and Caucasoid.

Adolescent↗
PubMed2004

Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene.

Progressive osseous heteroplasia (OMIM 166350) is a rare autosomal dominant condition that presents in childhood as dermal ossification and may progress deeper to involve subcutaneous fat and connective tissue. Recently, paternally inherited inactivating mutations in the GNAS1 gene on chromosome 20q13 have been implicated in the pathogenesis, although sporadic cases have also been reported. We report a 9-year-old British Chinese girl with progressive osseous heteroplasia resulting from a de novo missense mutation (W281R) in the GNAS1 gene. She is of small stature (0.4th centile) and started to develop skin lesions at the age of 9 months. These have been confirmed histologically as osteoma cutis. She is of normal intelligence and development and has no dysmorphic features. The GNAS1 gene exhibits imprinting and maternally inherited mutations have previously been shown to result in Albright's hereditary osteodystrophy (OMIM 103580) with pseudohypothyroidism type 1a, whereas paternally inherited mutations result in progressive osseous heteroplasia or the Albright's hereditary osteodystrophy phenotype with pseudopseudohypothyroidism (OMIM 300800). With only nine mutations of the GNAS1 gene reported so far in progressive osseous heteroplasia, this new mutation helps to extend further the genotype-phenotype correlation.

Child↗
PubMed2004

The role of extracellular matrix protein 1 in human skin.

Extracellular matrix protein 1 (ECM1) was first identified in 1994 as an 85-kDa glycoprotein secreted by a mouse osteogenic stromal cell line. Subsequently, the human homologue has been found to regulate endochondral bone formation, and to stimulate proliferation of endothelial cells and induce angiogenesis. However, a role for ECM1 in skin physiology and homeostasis has also emerged. Specifically, in 2002, loss-of-function mutations in the ECM1 gene were discovered to be the cause of the rare autosomal recessive genodermatosis, lipoid proteinosis. This inherited disorder is characterized clinically by skin and mucosal infiltration and scarring and histologically by disruption/duplication of basement membrane and widespread deposition of hyaline material in the dermis. Moreover, other recent studies have identified circulating autoantibodies against the ECM1 protein in most patients with lichen sclerosus, a common chronic inflammatory condition that shares some clinicopathological features with lipoid proteinosis. ECM1 thus serves as a target antigen in both an inherited and an acquired skin disorder. Within the epidermis, ECM1 has a role in the control of keratinocyte differentiation. Within the dermis, ECM1 binds to the major heparan sulphate proteoglycan, perlecan. In this way, ECM1 may act as a "biological glue" in the dermis, helping to regulate basement membrane and interstitial collagen fibril macro-assembly and growth factor binding. ECM1 may also have a role in other acquired skin disorders and physiological skin changes including scarring, wound healing and skin ageing, although this remains to be determined.

Cell Division↗
PubMed2004

Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Although the precise aetiology of lichen sclerosus is unknown, evidence for an autoimmune basis to the disorder is emerging. Indeed, circulating IgG autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been demonstrated in the sera of about 75% of affected individuals. To assess this humoral immune response further, immunoblotting was performed using bacterial recombinant proteins spanning different domains of the ECM1 protein. The aim was to identify autoantibody-reactive sites recognized by 90 lichen sclerosus sera. The subclass distribution of anti-ECM1 IgG autoantibodies was also determined in 54 lichen sclerosus sera. Immunoblotting showed that the IgG autoantibodies from lichen sclerosus patients recognize multiple antigenic reactive sites on the ECM1 protein within both the amino terminus (50/90, 55.6%) and the protein loop cysteine-rich repeat domains (54/90, 60%), although few sera (7/90, 7.8%) had antibodies to the carboxyl terminus of ECM1. IgG subclass analysis revealed that the anti-ECM1 autoantibodies belong predominantly to the IgG(2) subclass (48/54, 88.9%), either IgG(2) alone (28/54, 51.9%) or in combination with one or more other IgG subclasses. No correlation was found between the site(s) of the ECM1 epitopes or the anti-ECM1 IgG profile and any specific clinical parameters. Nevertheless, characterization of anti-ECM1 antibodies does provide further insight into humoral immune responses and understanding disease mechanisms in lichen sclerosus.

Adult↗
PubMed2004

Ectodermal dysplasia showing clinical overlap between AEC, Rapp-Hodgkin and CHAND syndromes.

The ectodermal dysplasias represent a complex collection of congenital abnormalities of skin, hair, teeth, nail, and sweat gland development, many of which have overlapping clinical features. In this report, we describe a 7-year-old girl, born to clinically normal parents, with ankyloblepharon, cleft lip/palate and hair abnormalities, features resembling the autosomal dominant disorder, ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome, which results from mutations in the sterile-alpha motif domain of the gene encoding the transcription factor, p63. However, direct sequencing of the p63 gene in this individual did not reveal any pathogenic sequence variants. Moreover, two of her paternal cousins were discovered to have similar congenital ectodermal anomalies, raising the alternative possibility of an autosomal recessive pattern of inheritance. Furthermore, all affected individuals lacked a history of erosive scalp dermatitis that is usually characteristic of AEC syndrome. Instead, the scalp hair was coarse and wiry. In addition, another atypical feature, hypohidrosis, was present. Collectively, the clinical features also resembled Rapp-Hodgkin syndrome, Bowen-Armstrong syndrome and CHAND syndrome, but did not appear to fit neatly with any one particular disorder. This case highlights the difficulties in trying to classify the ectodermal dysplasia syndromes on clinical features alone.

Child↗
PubMed2004

ADULT ectodermal dysplasia syndrome resulting from the missense mutation R298Q in the p63 gene.

Several ectodermal dysplasia syndromes have been shown to result from mutations in the gene that encodes the transcription factor p63. We describe an 11-year-old boy, with clinically normal parents, who had a developmental disorder that resembled EEC (ectrodactyly ectodermal dysplasia-clefting) syndrome (OMIM 604292). He had ectrodactyly and missing middle fingers bilaterally, onychodysplasia, hypodontia with missing teeth, hypohidrosis and lacrimal duct obstruction. DNA sequencing disclosed a heterozygous G-->A substitution at nucleotide 893, that converts an arginine residue (CGA) to glutamine (CAA), the mutation being designated R298Q. This mutation occurs within the DNA-binding domain of p63, and is close to many of the published EEC syndrome mutations. However, R298Q has been described once previously in a large German pedigree, not with EEC syndrome, but another ectodermal dysplasia disorder, ADULT (acro-dermato-ungual-lacrimal-tooth) syndrome (OMIM 103285). Further clinical assessment in our patient revealed that, apart from not having cleft lip and/or palate, he had an exfoliative dermatitis of his hands and feet, and some freckling on his face and shoulders. Collectively, these features support a diagnosis of ADULT syndrome. This study has identified a specific genotype-phenotype correlation in a rare ectodermal dysplasia syndrome and the findings are useful in improving genetic counselling in this family.

Base Sequence↗
PubMed2004

Severe acute respiratory syndrome in Singapore.

AIMS: To describe the epidemiological and clinical features of paediatric severe acute respiratory syndrome (SARS) in Singapore. METHODS: The following data were retrospectively collected from the case records of all 71 patients (aged 7 months to 14 years) admitted from 23 March to 22 May 2003 to the SARS paediatric unit: patient demographics, contact history, clinical features, physiological parameters, investigations, treatment, and outcome. Using WHO criteria there were seven probable (P), 23 suspect (S), and 41 observe (O) cases. RESULTS: Compared to the O cases P patients had a longer mean duration of fever (3.66 (SD 2.3) v 8.57 (SD 2.44) days), lower mean thrombocytopenia (248.3 (SD 82.7) v 173.7 (SD 49.0)x10(9)/l), leucopenia (8.19 (SD 4.45) v 3.06 (SD 1.02)x10(9)/l), lymphopenia (2.79 (SD 1.97) v 1.44 (SD 0.75)x10(9)/l), and neutropenia (4.48 (SD 2.88) v 1.24 (SD 0.43)x10(9)/l). Chest auscultation was abnormal in 71% of P patients, with mild crepitations detected. All had abnormal chest radiographs versus 39% of S cases, and 27% of O cases. CONCLUSIONS: There are no distinguishing clinical features of paediatric SARS. The diagnosis is suggested by the paucity of clinical signs with an abnormal chest radiograph, and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia.

Adolescent↗
PubMed2003

Cutaneous Waldenström's macroglobulinaemia.

We report a case of Waldenström's macroglobulinaemia that presented with infiltrated skin nodules and plaques but without systemic symptoms. Cutaneous manifestations such as purpura, oedema, urticaria and ulceration may be seen in Waldenström's macroglobulinaemia and are a consequence of hyperviscosity, cryoglobulinaemia and/or tissue deposition of immunoglobulins. Direct cutaneous infiltration by neoplastic lymphoid cells is less common, and very rare as the initial presentation of Waldenström's macroglobulinaemia.

Aged↗
PubMed2003

Molecular basis of lipoid proteinosis in a Libyan family.

Lipoid proteinosis is an autosomal recessive condition associated with variable scarring and infiltration of skin and mucosae. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1) on 1q21. Extracellular matrix protein 1 has important physiological and biological roles in aspects of epidermal differentiation, binding of dermal collagens and proteoglycans, and in regulation of angiogenesis. Thus far pathogenic mutations have been described in 16 different families with lipoid proteinosis throughout the world. In this report, we describe the clinico-pathological features of a 10-year-old boy with lipoid proteinosis from a consanguineous Libyan family. By direct sequencing of the affected individual's genomic DNA, we identified a homozygous nonsense mutation in exon 2 of the ECM1 gene, Q32X. This mutation is the most 5' of all ECM1 mutations described thus far and is predicted to ablate the ECM1a, ECM1b and ECM1c splice variants of the ECM1 gene and to result in a severe clinical phenotype. Sequencing of DNA from the affected individual's five siblings revealed that four were heterozygous carriers of Q32X, findings that have important implications for genetic counselling given the high frequency of consanguineous marriages in Libya.

Child↗
PubMed2001

Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma.

AIMS: Florid vasoproliferative processes are uncommon in the thyroid gland. We report three cases of an unusual vasoproliferation involving the capsular blood vessels of thyroid carcinoma. METHODS AND RESULTS: The histological diagnoses of the three cases were made on conventional histological sections. Two cases were minimally invasive follicular carcinomas and one case was an encapsulated variant of papillary carcinoma. Some blood vessels in the tumour fibrous capsule were filled with spindly cellular proliferations forming irregular vascular clefts and papillae. Immunohistochemical studies for CD31, CD34 and muscle-specific actin confirmed that the spindly cells were mostly endothelial cells variably supported by pericytes. CONCLUSION: This peculiar intravascular endothelial hyperplasia by itself should not be mistaken for vascular invasion by tumour, but evidence of malignancy must be diligently sought by extensive sampling because the lesion has thus far been consistently associated with malignant thyroid neoplasms.

Actins↗