Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong.

The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cut-offs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month-74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5th-95th percentile reference intervals of TREC and KREC levels (expressed in copies per µL blood and copies per 106 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9-12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.

Paediatric case series of drug reaction with eosinophilia and systemic symptoms (DRESS): 12-year experience at a single referral centre in Hong Kong and the first reported use of infliximab.

Summary: DRESS (drug reaction with eosinophilia and systemic symptoms) is a rare but potentially life-threatening disorder characterized by fever, skin eruption, haematological abnormalities and multi-organ dysfunction after drug exposure. The pathophysiology is thought to be related to interactions between culprit drugs, viral reactivation and T-lymphocytes activation. We report 4 paediatric patients with DRESS who were treated at our centre over the past 12 years. Most cases improved after corticosteroids. Other immunosuppressive medications were attempted in refractory cases with varied outcomes. Patient 3 was the first reported case that involved the use of infliximab, a TNF-α inhibitor, for DRESS. Although clinical efficacy was not observed for this one patient, a previous study demonstrated that patients with DRESS, disease progression and HHV-6 reactivation had elevated pre-treatment TNF- α and IL-6 levels. Further research is needed to explore the role of these cytokines in DRESS.

Reliability of acute illness dihydrorhodamine-123 testing for chronic granulomatous disease.

BACKGROUND: Dihydrorhodamine (DHR) flow cytometric analysis is used to evaluate granulocyte oxidative bursts and is the test of choice for the diagnosis of chronic granulomatous disease (CGD). We present the clinical and DHR test profiles of five subjects assessed during and after acute illness. METHODS: This was a retrospective report of the findings of five out of a total of one hundred and seventeen patients, whose blood was sent to the laboratory for dihydrorhodamine-123 flow cytometry testing between January 2005 and December 2010. Using whole blood technique and stimulation using phorbol myristate acetate, the results of DHR were expressed as stimulation index and coefficient of variation of histograms of stimulated cells and compared with healthy controls. DHR tests were repeated when the patients had recovered and were clinically well. RESULTS: These five patients showed abnormal DHR test results during their acute illness, with a stimulation index (SI) lower (p = 0.009) and coefficient of variation (CV) higher (p = 0.009) than controls. The DHR profiles repeated when patients had recovered showed normalization of tests with no significant difference for SI (p = 0.602) and CV (p = 0.917) compared to controls. Wilcoxon Signed Rank tests showed a significant improvement in SI (p = 0.043) and CV (p = 0.043) upon recovery. On follow up, all five patients were well, with no further severe or atypical infections. CONCLUSIONS: DHR may be transiently abnormal during acute illness, and may therefore not be reliable when assessed during an acute illness. If these subjects had CGD, it would be of a hypomorphic variant that has not previously been described.

Foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema.

OBJECTIVE: We examined the hypothesis that foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema. METHODS. The study was a population-based cross-sectional survey of Hong Kong Chinese children aged ≤14 years carried out in 2005 to 2006. RESULTS. Foetal exposure to maternal passive smoking was significantly associated with wheeze ever (OR 2.05; 95% CI 1.58-2.67), current wheeze (OR 2.06; 95% CI 1.48-2.86), allergic rhinitis ever (OR 1.22; 95% CI 1.09-1.37), and eczema ever (OR 1.61; 95% CI 1.38-1.87). Foetal exposure to maternal active smoking was significantly associated with asthma ever (OR 2.10; 95% CI 1.14-3.84), wheeze ever (OR 2.46; 95% CI 1.27-4.78), and current wheeze (OR 2.74; 95% CI 1.24-6.01) but not with allergic rhinitis ever (OR 1.01; 95% CI 0.70-1.46) or eczema ever (OR 1.38; 95% CI 0.87-2.18). The dose response relationship between wheeze ever and current wheeze with increasing exposure, from no exposure to maternal passive smoking and then to maternal active smoking, further supports causality. CONCLUSION. There is significant association between foetal exposure to maternal passive smoking and maternal active smoking with childhood asthma and related atopic illnesses. Further studies are warranted to explore the potential causal relationship.

Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn's disease.

Inflammatory bowel disease is well recognized for a strong genetic involvement in its pathogenesis. Homozygous mutations in interleukin-10 receptor 1 (IL-10R1) identified by linkage analysis were shown to be involved in this disorder. However, the underlying molecular mechanism and the causal nature of the mutations in the disease process remain to be clarified. In this study, using whole exome sequencing, we identified novel compound heterozygous missense mutations in the extracellular domain of IL-10R1 in a Crohn's disease patient from a non-consanguineous family. These mutations did not affect IL-10R1 expression, nor IL-10 binding. However, they abrogated IL-10R1 phosphorylation induced by IL-10, therefore leading to impaired STAT3 activation and suppression of inflammatory responses. After reconstitution with wild-type IL-10R1, the patient cells showed fully restored IL-10R function including IL-10-induced STAT3 activation and expression of suppressor of cytokine signaling 3. Thus, our results demonstrated that the mutations in IL-10R1 extracellular domain impair IL-10R1 activation rather than IL-10 binding, indicating these residues are important in IL-10 signal transduction through IL-10R1. The reconstitution data also confirmed the causality of the IL-10R1 mutations.

A novel CYBB mutation with the first genetically confirmed case of chronic granulomatous disease in South Africa.

A case of a child with chronic granulomatous disease (CGD) presenting with recurrent mycobacterial infections and invasive Aspergillus fumigatus disease is described. Genetic analysis confirmed X-linked CGD with a novel mutation in exon 10 of the CYBB gene - the first South African report of genetically confirmed CGD.

Detection of free living amoebae, Acanthamoeba and Naegleria, in swimming pools, Malaysia.

This study reports the detection of Acanthamoeba and Naegleria species in 14 swimming pools around Petaling Jaya and Kuala Lumpur, Malaysia. Sampling was carried out at 4 sites (the platforms (P), wall (W), 1 meter from the wall (1) and middle (2)) of each swimming pool. These free living amoebae (FLA) were detected under light and inverted microscopes after being cultured on the surface of non-nutrient agar lawned with Escherichia coli. Acanthamoeba species were detected in higher number of culture plates from all sampling sites of all the swimming pools. While Naegleria, were detected in fewer culture plates at 3 sampling sites (absent at site P) of 8 swimming pools. This suggested that the thick double-walled cysts of Acanthamoeba were more resistant, thus remaining viable in the dry-hot areas of the platforms and in chlorinated water of the swimming pools whereas Naegleria cysts, that are fragile and susceptible to desiccation, preferred watery or moist areas for growth and proliferation. The prevalence of both FLA was highest at site W (76.2%), followed by site 1 (64.7%), lowest at site 2 (19.4%), and could be detected at all 3 sampling levels (top, middle and bottom) of these 3 sites. The surface of site W might act as a bio-film that accumulated all kinds of microbes providing sufficient requirement for the FLA to develop and undergo many rounds of life cycles as well as moving from top to bottom in order to graze food. Other factors such as human activities, the circulating system which was fixed at all swimming pools, blowing wind which might carry the cysts from surroundings and the swimming flagellate stage of Naegleria could also contribute to the distribution of the FLA at these sampling sites. Both FLA showed highest growth (80.4%) at room temperature (25-28 ºC) and lesser (70.0%) at 37 ºC which might be due to the overgrowth of other microbes (E. coli, fungi, algae, etc). While at 44 ºC, only Acanthamoeba species could survive thus showing that our swimming pools are free from potentially pathogenic Naegleria species. However, further study is needed in order to confirm the virulence levels of these amoebae isolates.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 x 10(-9); TNFSF4, rs844648, OR=1.22, P=2.47 x 10(-3); TNFSF4, rs2205960, OR=1.30, P=2.41 x 10(-4)). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 x 10(-8), respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Quality of life in patients with transfusion-dependent thalassemia after hematopoietic SCT.

In this cross-sectional study, we compared the quality of life (QOL) in transfusion-dependent thalassemic patients who survived matched sibling hematopoietic SCT (HSCT, n=24) with patients treated conventionally with transfusion and iron chelation (n=74). WHOQOL-BREF(HK) and PedsQL questionnaires were administered to patients aged >18 years and 5-12 years, respectively. Patients aged 12-18 years received both questionnaires. WHOQOL-BREF(HK) revealed post transplant patients rated overall health better than those treated conventionally (score 3.67 vs 3.06, P=0.01). They are less dependent on medical aids (3.87 vs 2.96, P=0.006), having higher activity level (4.00 vs 3.36, P=0.026) and better personal relationships (4.13 vs 3.69, P=0.014). Physical health domain score was better (75.20 vs 63.94, P=0.007). These differences remained significant after adjustment for comorbidities. PedsQL revealed post transplant patients rated better for running (3.53 vs 2.72, P=0.001) and sports (3.20 vs 2.64, P=0.038), even after adjustment for comorbidities, but were less satisfied for school absence to attend hospital (2.53 vs 3.29, P=0.03). Post transplant patients were significantly more likely to consider marriage (100 vs 75.7%, P=0.033), but not childbearing (66.7 vs 51.4%, P=0.28). In conclusion, transplanted thalassemic patients enjoy better QOL, mainly in physical health, compared with conventionally treated patients. This information is important to patients considering HSCT.

Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation.

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age < or =2 years at transplant (odds ratio (OR)=5.25, P=0.011), BU-CY conditioning (OR=5.16, P=0.001), thalassemia major (OR=3.97, P=0.015), platelet engraftment beyond day +21 (OR=8.67, P=0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P=0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR)=23.6, P=0.006), hepatic and cutaneous GVHD (HR=8.15, P=0.038), maximal weight gain >9% (HR=6.81, P=0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 micromol l(-1) (HR=13.6, P=0.016), day +21 bilirubin >200 micromol l(-1) (HR=33.9, P=0.001), and rise of bilirubin >15 micromol l(-1) per day within the first week (HR=19.8, P=0.006). Mortality was substantially higher if >3 predictors were present (HR=33.9, P=0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.

Association between RANTES functional polymorphisms and tuberculosis in Hong Kong Chinese.

Chemokines play a major role in leukocyte recruitment during the formation of tuberculous granulomas. We studied the association between genetic polymorphisms of three chemokines, monocyte chemoattractant protein-1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha (MIP-1alpha), and tuberculosis (TB). The distribution of five functionally significant single-nucleotide polymorphisms (SNPs), MCP-1 -2518A/G, RANTES -403G/A, -28C/G and In1.1T/C as well as MIP-1alpha +459C/T was not found to be different between patients with TB and healthy control subjects of the Hong Kong Chinese population. However, differences in linkage disequilibrium (LD) of the SNPs of RANTES and in distribution of the haplotypes of RANTES between patients with TB and healthy controls (P<0.0001) were found. Two risk haplotypes of RANTES, A-C-T and G-C-C, at positions -403, -28 and In1.1, respectively, were identified. Furthermore, combining the genotypes of RANTES -403 and In1.1, two diplotypes GA/TT (P<0.001) and GG/TC (P<0.0001) showed strong association with TB. Our findings support the association between RANTES functional polymorphisms and TB.

Primary immunodeficiency in Hong Kong and the use of genetic analysis for diagnosis.

OBJECTIVES: To review the management of primary immunodeficiency and discuss recent advances in genetic analysis. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Children diagnosed with primary immunodeficiency and followed up in the immunology clinic during the period 1988 to 2003. MAIN OUTCOME MEASURES: Demographic data, co-morbidities and treatment of patients, outcome and complications; identification of disease by genetic mutations. RESULTS: Medical records of a total of 117 patients (72 male, 45 female) diagnosed with primary immunodeficiency in the Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong during the past 15 years (1988-2003) were reviewed. All patients were followed up in the immunology clinic. Some patients had been referred from the private sector or other hospitals for immunological workup. Six categories of primary immunodeficiency were identified: predominantly humoral defect (n=50), predominantly cellular defect (n=22), combined humoral and cellular defect (n=5), phagocytic defect (n=18), complement disorders (n=4), and others (n=18). Although infection was the underlying cause of most co-morbidities and mortality, autoimmune (n=7) and allergic (n=23) manifestations were common. In addition, three patients developed lymphoma. Recent advances in the genetic diagnosis of several types of primary immunodeficiency were also reviewed: X-linked Wiskott-Aldrich syndrome, X-linked chronic granulomatous disease, X-linked agammaglobulinaemia, X-linked lymphoproliferative syndrome, leukocyte adhesion disease type I, and X-linked hyperimmunoglobulin M syndrome. This provides an invaluable means of understanding the molecular basis of primary immunodeficiency and has important clinical applications. CONCLUSIONS: Co-morbidities like autoimmune disease and allergic disease are common in patients with primary immunodeficiency and should be carefully evaluated. Likewise, a diagnosis of primary immunodeficiency should be considered when evaluating patients with these conditions. Rapid progress in the field of molecular genetics will enable definite and early diagnosis, and more importantly, potential curative therapy to be administered.

Use of midazolam and ketamine as sedation for children undergoing minor operative procedures.

OBJECTIVES: We used intravenous midazolam and ketamine for children undergoing minor operative procedures with satisfactory results. We aimed to further evaluate its efficacy and adverse effects in pediatric ward setting. METHODS: This was a prospective study of all children undergoing minor operations with sedation in our pediatric general and oncology wards from July 1998 to June 1999. The procedures included lumber puncture+/-intrathecal chemotherapy, bone marrow aspiration+/-trephine biopsy, central venous catheter removal, skin biopsy, or their combination. All sedation procedures were started with midazolam 0.1 mg/kg and ketamine 1 mg/kg; they were increased gradually to 0.4 and 4 mg/kg, respectively, if necessary. Heart rate and SaO2 were continuously monitored. RESULTS: Altogether, 369 minor operations were performed in 112 patients (male:female=2:1, median age 6 years, range 5 months-17 years). All achieved adequate sedation, with 96% within 30 s and 75% required just the starting dose. Younger children required a higher dosage (p=0.003 for midazolam, p<0.001 for ketamine). The median recovery time was 87 min, with no association with age, sex, or dosage of sedation, but was longer in patients having hallucination (p=0.001). Adverse effects included tachycardia (27.9%), increased secretion (17.6%), agitation (13.6%), nausea and vomiting (9.2%), hallucination (8.7%), desaturation (8.4%), and cataleptic reaction (0.8%). All desaturation episodes were transient and responded to oxygen supplement alone. None developed bronchospasm or convulsion. Some adverse effects were dose-related. Half of the children who received 0.3 mg/kg midazolam developed desaturation. CONCLUSIONS: Intravenous midazolam-ketamine can provide rapid, effective, and safe sedation for children undergoing minor operations in ward setting. Adverse effects are mild. Midazolam above 0.3 mg/kg should be used with caution.

Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation.

We assayed helper T-lymphocyte precursor frequencies (HTLPf), interferon (IFN)-gamma-producing cell frequencies (IFN-gammaPf) and CTL precursor frequencies (CTLPf) to see if they could predict the severity of acute graft-versus-host disease (aGVHD) and disease relapse after transplantation. In all, 48 bone marrow transplantation (BMT) patients and their HLA-identical sibling (n=29) or matched unrelated donors (MUD) (n=19) were recruited. HTLPf, IFN-gammaPf and CTLPf were measured using a limiting dilution assay (LDA). Patients were followed prospectively to assess the severity of aGVHD and the status of the primary disease after BMT. High (>5 x 10(-6)) HTLPf, CTLPf and IFN-gammaPf were significantly associated with the occurrence and severity of aGVHD in patients who received transplants from HLA-identical sibling. Among patients receiving BMT from MUD, HTLPf and CTLPf, but not IFN-gammaPf, were associated with aGVHD. Five patients had disease relapse post-BMT and the risk was not significantly associated with HTLPf, CTLPf or IFN-gammaPf. Patients with high (>5 x 10(-6)) HTLPf, IFN-gammaPf or CTLPf before BMT are at higher risk of developing aGVHD after transplantation from both matched sibling donors and MUD. Whether these parameters can predict disease relapse would have to be investigated with a larger cohort of patients.

Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?

BACKGROUND: In 1997, the first documented instance of human respiratory disease and death associated with a purely avian H5N1 influenza virus resulted in an overall case-fatality rate of 33%. The biological basis for the severity of human H5N1 disease has remained unclear. We tested the hypothesis that virus-induced cytokine dysregulation has a role. METHODS: We used cDNA arrays and quantitative RT-PCR to compare the profile of cytokine gene expression induced by viruses A/HK/486/97 and A/HK/483/97 (both H5N1/97) with that of human H3N2 and H1N1 viruses in human primary monocyte-derived macrophages in vitro. Secretion of tumour necrosis factor alpha (TNF alpha) from macrophages infected with the viruses was compared by ELISA. By use of naturally occurring viral reassortants and recombinant viruses generated by reverse genetic techniques, we investigated the viral genes associated with the TNF-alpha response. FINDINGS: The H5N1/97 viruses induced much higher gene transcription of proinflammatory cytokines than did H3N2 or H1N1 viruses, particularly TNF alpha and interferon beta. The concentration of TNF-alpha protein in culture supernatants of macrophages infected with these viruses was similar to that induced by stimulation with Escherichia coli lipopolysaccharide. The non-structural (NS) gene-segment of H5N1/97 viruses contributed to the increase in TNF alpha induced by the virus. INTERPRETATION: The H5N1/97 viruses are potent inducers of proinflammatory cytokines in macrophages, the most notable being TNF alpha. This characteristic may contribute to the unusual severity of human H5N1 disease.

Influenza A infection is an important cause of febrile seizures.

OBJECTIVES: To compare the incidence of febrile seizures in children hospitalized for influenza A infection with parainfluenza and adenovirus infection and to examine the hypothesis that children hospitalized for influenza A (variant Sydney/H3N2) during the 1998 season in Hong Kong had more frequent and refractory seizures when compared with other respiratory viruses, including the A/Wuhan H3N2 variant that was present in the previous year. METHODS: Medical records of children between 6 months and 5 years of age admitted for influenza A infection in 1998 were reviewed. For comparison, records of children of the same age group with influenza A infection in 1997, and with parainfluenza and adenovirus infections between 1996 and 1998 were reviewed. Children who were afebrile or who had an underlying neurologic disorder were excluded. RESULTS: Of children hospitalized for influenza A in 1998 and 1997, 54/272 (19.9%) and 27/144 (18.8%) had febrile seizures, respectively. The overall incidence of febrile seizures associated with influenza A (19.5%) was higher than that in children hospitalized for parainfluenza (18/148; 12.2%) and adenovirus (18/199; 9%) infection, respectively. In children who had febrile seizures, repeated seizures were more commonly associated with influenza A infection than with parainfluenza or adenovirus infection (23/81 [28%] vs 3/36 [8.3%], odds ratio [OR] 4.3, 95% confidence interval: 1.2 to 15.4). Alternatively, children with influenza A infection had a higher incidence (23/416, 5.5%) of multiple seizures during the same illness than those with adenovirus or parainfluenza infection (3/347, 0.86%; OR 6.7, 95% confidence interval: 2.0-22.5.) The increased incidence of febrile seizures associated with influenza A was not attributable to differences in age, gender, or family history of febrile seizure. Multivariate analysis, adjusted for peak temperature and duration of fever, showed that hospitalized children infected with infection A had a higher risk of febrile seizures than those who were infected with parainfluenza or adenovirus (OR 1.97). Influenza A infection was a significant cause of febrile seizure admissions. Of 250 and 249 children admitted to Queen Mary Hospital for febrile seizures in 1997 and 1998, respectively, influenza A infection accounted for 27 (10.8%) admissions in 1997 and 54 (21.7%) in 1998. During months of peak influenza activity, it accounted for up to 35% to 44% of febrile seizure admissions. In contrast, parainfluenza, adenovirus, respiratory syncytial virus, and influenza B had a smaller contribution to hospitalizations for febrile seizures, together accounting for only 25/250 (10%) admissions in 1997 and 16/249 (6.4%) in 1998. CONCLUSION: The influenza A Sydney variant (H3N2) was not associated with an increased risk of febrile seizures when compared with the previous influenza A Wuhan variant (H3N2) or H1N1 viruses. However, in hospitalized children, influenza A is associated with a higher incidence of febrile seizures and of repeated seizures in the same febrile episode than are adenovirus or parainfluenza infections. The pathogenesis of these observations warrants additional studies. Complex febrile seizures, particularly multiple febrile seizures at the time of presentation, have been thought to carry an adverse long-term prognosis because of its association with a higher incidence of epilepsy. Repeated febrile seizures alone, particularly if associated with influenza A infection, may not be as worrisome as children with complex febrile seizures because of other causes, which requires additional investigation. This may subsequently have an impact on reducing the burden of evaluation in a subset of children with complex febrile seizures.

Different allelic frequencies of several cytokine genes in Hong Kong Chinese and Swedish Caucasians.

It has been shown that cytokine gene polymorphisms are important in the regulation of the level of cytokine production that may affect the development and extent of inflammatory diseases and transplant rejections. The frequency of the -308 TNFA, -383 TNFR1, -1087 IL10 and codon 25 TGFB1 alleles were analysed in two different ethnic groups: Chinese from Hong Kong and Caucasians from western Sweden. Significant differences in the occurrence of the analysed alleles were shown between the two populations. The most profound difference was found in the frequency of the A/A genotype at the -1087 position of IL10 gene (18% in Caucasians and 89% in Chinese, P < 0.0001, both for the genotype and allele frequencies) and less although statistically significant for other investigated genes. The noted differences in the frequency of functionally important alleles of cytokine genes may have consequences for the mode of appearance and outcome of certain diseases in individuals of different ethnicity.

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.