Amplification of AML1 in acute lymphoblastic leukemia is associated with a poor outcome.
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Child↗
Biomedical subjects
K L Cheung
Publications and source records attributed to K L Cheung.
A rapid-release 50-mg tablet-based 13C-urea breath test for the diagnosis of Helicobacter pylori infection.
BACKGROUND: Recently, a rapid-release 100-mg 13C-urea tablet with citrate supplement (Diabact UBT) showed excellent performance in a European population. AIM: To investigate the accuracy of a 50-mg tablet-based 13C-urea breath test protocol. METHODS: : Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-Urea breath test was performed using a 50-mg 13C-urea tablet (Diabact UBT) and compared with the gold standard (rapid urease test and histology). Baseline, 10-min, 20-min and 30-min breath samples were collected in all cases. The cut-off values at each measurement interval were determined by three standard deviations above the mean excess delta 13CO2 excretion of Helicobacter pylori-negative patients. RESULTS: Two hundred patients (150 before therapy and 50 after therapy) were available for analysis, with a mean age of 48.4 years, and 99 patients (50%) were H. pylori positive. The sensitivity and specificity of the 50-mg tablet-based 13C-urea breath test at 10 min, 20 min and 30 min were 100% and 98%, 100% and 100%, and 100% and 98%, respectively. CONCLUSION: A 20-min, 50-mg tablet-based 13C-urea breath test (Diabact UBT) protocol is highly accurate for the diagnosis of H. pylori infection.
Adolescent↗
Infection control for SARS in a tertiary neonatal centre.
The Severe Acute Respiratory Syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus, which can readily spread in the healthcare setting. A recent community outbreak in Hong Kong infected a significant number of pregnant women who subsequently required emergency caesarean section for deteriorating maternal condition and respiratory failure. As no neonatal clinician has any experience in looking after these high risk infants, stringent infection control measures for prevention of cross infection between patients and staff are important to safeguard the wellbeing of the work force and to avoid nosocomial spread of SARS within the neonatal unit. This article describes the infection control and patient triage policy of the neonatal unit at the Prince of Wales Hospital, Hong Kong. We hope this information is useful in helping other units to formulate their own infection control plans according to their own unit configuration and clinical needs.
Cross Infection↗
Objective measurement of remission and progression in metastatic breast cancer by the use of serum tumour markers.
Measurement of remission and progression in metastatic breast cancer by the use of serum tumour markers is simple, objective, reproducible and cost effective. The most widely used markers are a MUC1 mucin (e.g. measured as CA15.3) and CEA. A combination of markers is more sensitive than using a single marker. When CA15.3, CEA and ESR are used as a panel of serum markers in monitoring therapeutic response, over 90% of patients are biochemically assessable. A biochemical index score comprising these three markers has been devised retrospectively, validated prospectively, in a single centre and in a multicentre study. Biochemical assessment by serum markers correlates with clinical/radiological (UICC) assessment and often pre-dates remission and progression shown by UICC criteria. It is also the only validated method in monitoring metastatic breast cancer with disease unassessable by UICC criteria (e.g. sclerotic bone metastases, irradiated lesions). Future studies should aim at incorporating new markers (e.g. serum c-erbB2, markers of bone metabolism) to tailor different clinical situations, and at exploiting the use of serum markers to direct systemic therapy.
Biomarkers, Tumor↗
Editorial comment on 'Serum markers in breast cancer management'.
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Breast Neoplasms↗
Seven new mutations in the nicotinamide adenine dinucleotide reduced-cytochrome b(5) reductase gene leading to methemoglobinemia type I.
Cytochrome b(5) reductase (b5R) deficiency manifests itself in 2 distinct ways. In methemoglobinemia type I, the patients only suffer from cyanosis, whereas in type II, the patients suffer in addition from severe mental retardation and neurologic impairment. Biochemical data indicate that this may be due to a difference in mutations, causing enzyme instability in type I and complete enzyme deficiency or enzyme inactivation in type II. We have investigated 7 families with methemoglobulinemia type I and found 7 novel mutations in the b5R gene. Six of these mutations predicted amino acid substitutions at sites not involved in reduced nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FAD) binding, as deduced from a 3-dimensional model of human b5R. This model was constructed from comparison with the known 3-dimensional structure of pig b5R. The seventh mutation was a splice site mutation leading to skipping of exon 5 in messenger RNA, present in heterozygous form in a patient together with a missense mutation on the other allele. Eight other amino acid substitutions, previously described to cause methemoglobinemia type I, were also situated in nonessential regions of the enzyme. In contrast, 2 other substitutions, known to cause the type II form of the disease, were found to directly affect the consensus FAD-binding site or indirectly influence NADH binding. Thus, these data support the idea that enzyme inactivation is a cause of the type II disease, whereas enzyme instability may lead to the type I form.
Adult↗
Cross-species color banding in ten cases of myeloid malignancies with complex karyotypes.
Cross-species color banding is a multiple-color fluorescence in situ hybridization (FISH) technique using probes developed from other animal species. Hybridization to human metaphases produces color banding patterns specific for each homologous chromosome pair. The technique has been evaluated in a complementary manner with G-banding and chromosome painting in a series of 10 myeloid malignancies with complex or unresolved karyotypes. Color banding detected the majority of chromosomal abnormalities, which had been identified by G-banding and in each case revealed chromosomal changes that G-banding had not identified. Painting was necessary to confirm these abnormalities due to the limitation of only seven colors in the color-banded karyotype. At the same time, painting fortuitously uncovered cryptic abnormalities in 6 of 10 cases that had not been detected by color banding. Insertions were visible by painting only. This study has demonstrated that in the analysis of complex karyotypes, the application of color banding revealed the involvement of the long arm of chromosome 3, indicating a poor risk, in two cases not identified by G-banding. Therefore, these techniques applied together have revealed cryptic chromosomal abnormalities with prognostic significance, which in some cases may have implications for patient management.
Adolescent↗
Overview of common inherited metabolic diseases in a Southern Chinese population of Hong Kong.
BACKGROUND: The Joint metabolic clinic at the Prince of Wales Hospital was established in January 1997 to provide a comprehensive multi-disciplinary care to patients with inherited metabolic diseases (IMDs). Patients are referred from both within and outside our hospital. Until July, 2000, more than 40 patients and families with 20 different biochemical diagnoses attend the clinic for regular follow up. A pattern of more common IMDs among Hong Kong Chinese emerged from our case registry. In order to advance the understanding of Chinese metabolic diseases, we examined the molecular basis of those diseases with unique features in Chinese or were locally prevalent. Mutations were found in patients with primary carnitine deficiency, ornithine transcarbamylase deficiency, X-linked adrenoleukodystrophy, glutaric aciduria type I, and galactosemia. We also analyzed the mutations in multiple carboxylase deficiency and Niemann-pick type C on four families. CONCLUSIONS: Although IMDs are a significant cause of mortality and morbidity among pediatric patients, with a better understanding of the molecular genetics of these diseases, prenatal diagnosis of these common IMDs will be facilitated, which is currently the most effective way of controlling IMDs.
Fatty Acids↗
Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy.
We report the medium-term (median follow-up=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.
Adult↗
Selection of primary breast cancer patients for adjuvant endocrine therapy--is oestrogen receptor alone adequate?
Among 834 patients who had primary breast cancer treated by surgery without adjuvant systemic therapy, 363 had relapse treated by endocrine therapy alone. Patients with oestrogen receptor positive tumours (median: 70 vs. 45 months, p < 0.0001) or with non-progression at 6 months of therapy (median: 111 vs. 37 months, p < 0.0001) survived longer than those with oestrogen receptor negative tumours or with disease progression respectively, presumably due to the effect of therapy. On the other hand, the median disease-free interval, uninfluenced by therapy, showed a similar difference: oestrogen receptor positive versus negative = 29 versus 21 months, p < 0.005; non-progression versus progression = 40 versus 19 months, p < 0.0001. Patients with oestrogen receptor-positive tumours and non-progression at 6 months had the longest disease-free interval. The present study has established that there are factors, other than the oestrogen receptor, inherent in the primary tumour as reflected by the disease-free interval, which affect hormone sensitivity. Selection of adjuvant endocrine therapy based on the oestrogen receptor alone would deem inadequate. Further studies to elucidate other possible factors are warranted to refine the use of endocrine therapy, especially in the adjuvant setting when no indication of response is available.
Breast Neoplasms↗
The use of blood tumour markers in the monitoring of metastatic breast cancer unassessable for response to systemic therapy.
The role of blood tumour markers is established in the monitoring of response to systemic therapy for patients with metastatic breast cancer assessable by UICC criteria. This paper examines the use of marker measurements (in the form of a previously devised biochemical index score comprising CA15.3, CEA and ESR) in patients with metastatic lesions unassessable for response by UICC criteria. Of 218 patients with metastatic breast cancer treated over a 2-year period in the Nottingham Breast Unit, 43 patients (20%) had unassessable disease and 36 of them with blood marker results available were studied. Eighty-six per cent of patients were biochemically assessable. All patients who achieved biochemical response remained unassessable by UICC criteria. Twenty-two patients progressed initially or subsequently (after an initial biochemical response), either biochemically or by UICC criteria. Biochemical assessment completely paralleled UICC assessment in all eight patients who progressed by both assessments. Biochemical progression occurred ahead of UICC assessment in four of them with a median lead-time of 4.5 months. Biochemical assessment by blood tumour markers is useful in patients with metastatic breast cancer unassessable for response to systemic therapy. These findings need to be confirmed in a larger patient series.
Biomarkers, Tumor↗
Three further cases of t(8;14)(q11.2;q32) in acute lymphoblastic leukemia.
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Adult↗
Twenty-minute 50 mg 13C-urea breath test without test meal for the diagnosis of Helicobacter pylori infection in Chinese.
BACKGROUND: We have previously shown that the 75 mg 13C-urea breath test without citrate test meal is highly accurate for the diagnosis of Helicobacter pylori infection in Chinese subjects. A lower dose 50 mg 13C-urea breath test protocol with a sampling time at 20 min has not been validated previously. AIM: To investigate the accuracy of a 20-min 50 mg 13C-urea breath test protocol in Chinese subjects. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-urea breath test was performed using (a) 75 mg and 50 mg of 13C-urea on two separate days without a test meal, and (b) 50 mg of 13C-urea with 2.4 g citrate as test meal, and compared with the gold standard [rapid urease test (CLO test) and histology]. Baseline, 20-min and 30-min breath samples were collected in all cases. RESULTS: Two hundred and six patients were tested. The accuracy of the 50 mg 13C-urea breath test (no citrate) at 20 min and 30 min was 98%, comparable to that of the 50 mg 13C-urea breath test with citrate (99.1%) and the 75 mg 13C-urea breath test without citrate (100%). CONCLUSIONS: A 20-min 50 mg 13C-urea breath test without citrate produced highly accurate results for the diagnosis of Helicobacter pylori infection and is more economical and convenient for the Chinese population.
Adult↗
Preoperative hormone therapy trials for breast cancer.
Preoperative hormone therapy for breast cancer has the potential to downstage a primary tumour hence increasing operability as well as making breast conservation feasible. Whether it will achieve any clinically significant survival benefit remains to be elucidated. Preoperative hormone therapy, in contrast to neoadjuvant chemotherapy, produces less severe side effects and can be continued throughout the perioperative period. Presurgical studies have demonstrated anti-tumour effects of hormone therapy, e.g. down-regulation of ER. Current clinical trials have shown that, in patients with ER positive tumours, a response approaching 70% is reached in approximately three months using the traditional hormonal agent tamoxifen. The tumour seldom progresses during this period. New agents (such as third generation aromatase inhibitors and pure anti-oestrogens) may produce more profound and rapid responses. Future trials are required to identify factors other than ER to precisely predict response so that appropriate patients can be selected. The best agents, the ideal methods of monitoring response and the optimum duration of therapy also need to be identified. Clinical trials also need to test if pre- and perioperative hormone therapy is superior to conventional adjuvant hormone therapy in patients with early breast cancer.
Journal Article↗
Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: a randomized controlled study.
UNLABELLED: Infants requiring parenteral nutrition (n = 244) were randomized to receive either 1 (group 1, n = 121) or 0.0182 micromol/kg/d (group 2, n = 123) of manganese supplementation. The whole-blood manganese and serum direct bilirubin concentrations of the infants were monitored, as was the development of cholestasis (peak serum direct bilirubin concentration >50 micromol/L). Subgroup analysis was carried out on the data of 78 infants in group 1 and 82 in group 2 who had received manganese supplementation and more than three-quarters of their total daily fluid as parenteral nutrition for >14 d. Of all the infants randomized, the high manganese group (group 1) showed a trend towards developing higher peak whole-blood manganese concentration [group 1 versus group 2: median (interquartile range): 606.0 (421.0; 1005.0) vs 566.0 (336.0: 858.0); p=0.061] and higher peak serum direct bilirubin concentration [37.0 (10.5; 122.5) vs 19.0 (8.0; 112.5); p=0.153], but the differences between the 2 groups did not reach statistical significance. The 2 groups did not differ in terms of the occurrence of cholestasis during parenteral nutrition (63/121 vs 57/123; p=0.444). Subgroup analysis of infants who had received more than three-quarters of their total daily fluid as parenteral nutrition showed, however, that the high manganese group developed significantly higher whole-blood manganese concentration [743.5 (498.0; 1211.0) vs 587.0 (438.0; 982.0); p=0.037] and serum direct bilirubin concentration [84.0 (28.0; 170.0) vs 25.5 (9.0; 117.0): p < 0.001]. Although there was no significant difference in the occurrence of cholestasis (58/78 vs 49/82; p = 0.073), more infants in the high manganese group developed a more severe degree of direct hyperbilirubinaemia, with peak serum direct bilirubin >100 micromol/L (32/78 vs 20/82; p = 0.038). CONCLUSION: We conclude that the pathogenesis of parenteral nutrition-related cholestasis is probably multifactorial, and that high manganese intake is a significant contributory factor.
Cholestasis↗
Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants.
AIM: To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes. RESULTS: Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10 v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms. CONCLUSIONS: Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.
Double-Blind Method↗
Palpable asymmetrical thickening of the breast: a clinical, radiological and pathological study.
While management protocols for a discrete palpable breast lump are standardized in most centres, the approach to an area of palpable asymmetrical thickening in the breast has seldom been addressed. A diagnostic algorithm for palpable asymmetrical thickening of the breast was prospectively evaluated in 116 Oriental women, followed by a retrospective review of their mammograms and histology specimens. Most women (86%) were pre-menopausal and 82% complained of a lump. The thickening eventually resolved spontaneously in 93 (80%) women. None of these 93 women developed cancer at a median follow-up of 41 months. A total of 9 (7.8%) cancers were found in the series of 116 women, including two with a lobular component. The occurrence of cancer was more likely when the woman was older than 43 years or when the thickening was marked (p<0.04). Mammographic review showed correlation of the palpable thickening with localized increase in breast tissue density and/or microcalcifications in 18% of cases. Histology review suggested fibrosis as an explanation for the clinical presentation. Although most cases of thickening tend to resolve with time, a significant number of cancers present in this way. A diagnostic approach with early and liberal imaging and biopsy for high risk women is required.
Adult↗
Multiplex fluorescence in situ hybridization and cross species color banding of a case of chronic myeloid leukemia in blastic crisis with a complex Philadelphia translocation.
Exciting new techniques in molecular cytogenetics--namely, spectral karyotyping, multiplex fluorescence in situ hybridization (M-FISH), and cross species color banding--have been recently developed. An increasing number of reports demonstrate the success of these procedures in providing additional cytogenetic information--identifying marker chromosomes and revealing the presence of previously undetected chromosomal changes. However, these procedures have their limitations, and their absolute sensitivity in the accurate identification of subtle chromosomal abnormalities remains to be established. M-FISH and color banding have been applied to a case of chronic myeloid leukemia with a complex Philadelphia translocation involving chromosomes 9, 17, and 22, which had initially been identified from G-banded chromosome analysis. The abnormalities were confirmed by chromosome "painting" and specific probes. Although M-FISH and color banding revealed no additional cryptic chromosomal changes, this study has clearly demonstrated the success of these multiple color FISH approaches in the accurate characterization of a complex rearrangement with subtle abnormalities.
Adolescent↗