Ki Wai Chik

Partial neuroprotective effect of pretreatment with tanshinone IIA on neonatal hypoxia-ischemia brain damage.

Tanshinone IIA is a compound purified from the Chinese herb Danshen (Radix Salviae Miltiorrhiza Bge). The neuroprotective effect of tanshinone IIA was investigated in a neonatal rat model of hypoxia-ischemia brain damage. Hypoxia-ischemia encephalopathy was induced in rats at day 7 of postnatal age by ligation of the right common carotid artery, followed by 2 h of hypoxia. Tanshinone IIA (10 mg/kg, i.p.) was injected daily from day 2 before surgery for 9 or 16 d. Our results demonstrated significant and sustained brain damage in the hypoxia-ischemia– and vehicle-treated groups at 1 and 3 wk after surgery. Treatment with tanshinone IIA significantly reduced the severity of brain injury, as indicated by the increase in ipsilateral brain weight and neuron density, compared with those of sham-operated animals. The recovery of sensorimotor function and histology was observed in animals that received tanshinone IIA. The plasma of tanshinone IIA–treated rats exhibited higher antioxidant activities, as reflected by the oxygen radical absorbance capacity assay, compared with the vehicle-treated rats. In the neural progenitor cell line C17.2 that was subjected to 2,2′-azobis (2-amidino propane hydrochloride)–induced oxidative stress, tanshinone IIA increased cell viability and protected against mitochondrial damage (JC-1 assay). Our results suggest that tanshinone IIA has antioxidative activities and that treatment that is started before a hypoxic-ischemic insult is partially neuroprotective. Further studies are required to elucidate whether rescue treatment with tanshinone IIA is effective and to determine whether its protective effect is also associated with secondary cooling of the brain.

Epidemiology of respiratory syncytial virus infection among paediatric patients in Hong Kong: seasonality and disease impact

In a 5-year retrospective survey of respiratory syncytial virus (RSV) infections among hospitalized children, 1340 cases were identified of which, 98.4% were children < 5 years old with a male:female ratio of 1.5: 1. Most cases occurred from April to September showing a significant positive correlation with temperature and relative humidity. Community-acquired infections accounted for 92.5% of the cases with a mean hospital stay of 5 days. The estimated annual incidence of RSV infection requiring hospitalization was 2.5/1000 children < 5 years old with a mortality of 0.15% among hospitalized cases. On average, 248 children were admitted each year to the 1400-bed acute regional hospital accounting for an expenditure of HK S1.94 ((approximately US +/-0.25) million for hospitalization costs which equates to an annual cost in excess of HK

Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major: predominance of osteoporosis and desferrioxamine-induced bone dysplasia

6.67 (approximately US

Liver disease in transfusion dependent thalassaemia major

0.86) million for the whole of Hong Kong. An RSV vaccine should be a priority.

Immunogenicity of a two-dose regime of varicella vaccine in children with cancers

Objective: To study the radiographic skeletal changes in transfusion-dependent homozygous β-thalassaemia. Materials and methods: This was a retrospective review of radiographs of 41 homozygous β-thalassaemic patients over 3 years. These included 55 left hand radiographs for bone age, 37 chest radiographs, 7 scanograms of lower limbs, 8 knee radiographs and 3 skull radiographs. The radiographs were evaluated for the skeletal changes owing to medullary expansion, as well as for the skeletal dysplasia related to desferrioxamine therapy. The combined cortical width of the mid shaft of the second metacarpal was measured on left hand radiographs to assess osteoporosis. Results: Sixteen patients had radiographic evidence of desferrioxamine-induced bone dysplasia. These included metaphyseal sclerosis in long bone (n=16), irregular sclerosis at the costochondral junction (n=3) and platyspondyly (n= 1). Two patients had radiographic evidence of medullary expansion with widening of medulla and marked thinning of cortex in the tubular bones. Osteoporosis, as indicated by thinning of metacarpal cortex, was noted in 17 patients (8 with and 9 without desferrioxamine-induced bone dysplasia). Conclusions: With provision of the modern regime of regular transfusion and desferrioxamine chelation, desferrioxamine-induced bone dysplasia was a much more frequently detected radiographic abnormality in β-thalassaemia major than radiographic features owing to medullary expansion. Osteoporosis, as indicated by thinned metacarpal cortices, remained a frequent feature irrespective of the status of the skeletal dysplasia.

Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis.

Aims: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. Method: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). Results: One hundred patients were evaluated (median age 11.7 years, range 1.5–27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3–4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. Conclusion: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

Detection of micrometastasis of neuroblastoma to bone marrow and tumor dissemination to hematopoietic autografts using flow cytometry and reverse transcriptase-polymerase chain reaction.

Objective:  Live‐attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children.

Elevated Serum Interleukin-15 Level in Acute Graft-versus-host Disease After Hematopoietic Cell Transplantation

PURPOSE To evaluate the long-term brain metabolite changes on (1)H-MRS in acute lymphoblastic leukemia (ALL) patients who had intrathecal methotrexate (ITMTX) and cranial irradiation (CRT) for central nervous system (CNS) prophylaxis against CNS relapse. METHODS AND MATERIALS Thirty-seven ALL patients (12 females, 25 males) with history of ITMTX and CRT for CNS prophylaxis were studied. Age ranges at the time of diagnosis and at magnetic resonance examination were 0.8-13 years and 12-27 years, respectively. The interval since diagnosis was 5.6-19 years. T2-weighted and gradient-recalled echo (GRE) magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H-MRS) were performed to assess brain injury. RESULTS On MRI, 3 leukoencephalopathy (LEP) and 1 infarct were detected. Twenty-two patients had evidence of hemosiderin. On (1)H-MRS no statistically significant difference in choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cr was associated with LEP. A lower Cho/Cr (p = 0.006) and NAA/Cr (p = 0.078) was observed in brains with hemosiderin. Linear-regression analysis showed no statistically significant relationship between NAA/Cr or Cho/Cr with age at diagnosis, but there was a statistically significant decreasing trend of NAA/Cr and Cho/Cr with the interval since diagnosis. CONCLUSION Long-term brain injury in ALL survivors after CNS prophylaxis with ITMTX and CRT was reflected by decreasing NAA/Cr and Cho/Cr with the interval since diagnosis. The lower Cho/Cr associated with hemosiderin but not LEP suggested a different pathophysiology for these brain lesions.

Growth and endocrine function following bone marrow transplantation for thalassemia major.

The identification of neuroblastoma metastases to bone marrow (BM) is requisite in staging disease for risk‐adopted therapy. However, micrometastases were not elucidated fully.

Human neonatal blood: stem cell content, kinetics of CD34+ cell decline and ex vivo expansion capacity

Objective To correlate serum cytokine levels and the development of acute graft-versus-host disease (GVHD), the authors conducted a prospective study on serial measurements of interferon (IFN)-&ggr; and interleukin (IL)-10, IL-12 and IL-15. Methods The cytokines were measured in 27 subjects by enzyme-linked immunosorbent assay serially for the first 2 months after hematopoietic cell transplantation. Results Nineteen subjects with acute GVHD had significantly higher mean peak serum levels of IFN-&ggr; and IL-15 than the baseline levels at the start of conditioning. The peak level occurred soon after stem cell infusion and returned to the pretransplantation state in the second month. In contrast, there was lesser difference between the mean peak serum levels of IFN-&ggr;, IL-10, and IL-15 and the baseline level in the eight subjects without GVHD. The peak serum level for IL-15 was, in addition, significantly higher among GVHD subjects than those without GVHD in the first month posttransplantation. However, the level of IL-15 showed no correlation with the severity of GVHD. Conclusions These changes point to a possible role of systemic cytokine secretion in the development of acute GVHD. Elevated levels of IL-15 early in the posttransplant period could be a helpful laboratory predictor of acute GVHD.