Toxic exposures and haematological disorders.
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Hematologic Diseases↗
Biomedical subjects
T K Chan
Publications and source records attributed to T K Chan.
Intragenic dinucleotide repeats in factor VIII gene for the diagnosis of haemophilia A.
Two multi-allelic microsatellite polymorphisms within the factor VIII gene were studied in 138 Chinese subjects. The allele sizes detected were higher than those found in Caucasian populations, whereas the heterozygosity rates were lower, being 0.5370 for intron 13 and 0.4444 for intron 22 repeats respectively. Their usefulness in diagnosis was compared to other intragenic and extragenic RFLPs, using previous data on the same 31 unrelated haemophilia A families. These intragenic microsatellite repeat polymorphisms were only informative for 18/31 families (58%); however, with the combined use of all existing RFLPs, the cumulative informativeness would be 100%.
Asian People↗
Childhood acute lymphoblastic leukaemia and aplastic anaemia.
Aplastic anaemia (AA) can be associated with disorders that are known to exhibit clonal haematopoiesis, like paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It appears that the long term survivors of severe AA treated with immunosuppressive agents such as ATG have a continuing, late mortality caused by the evolution of clonal disorders which are not usually seen when bone marrow transplant is used. In children, typical AA may precede the onset of acute lymphoblastic leukemia (ALL). The aplastic phase is often transient and remission may be spontaneous or rapidly induced by steroid, and followed a few months later by acute leukaemia. This modality of presentation may be observed in up to 2-3% of all cases of paediatric ALL. A 13-year old girl who presented with two spontaneously reversible episodes of marrow aplasia has been reported recently. She developed ALL 8 months later. Southern analysis showed identical clonal immunoglobulin heavy chain gene rearrangement bands in her leukaemic cells as well as the marrow cells obtained at the two aplastic episodes. Hypoxanthine phosphoribosyltransferase polymorphism studies showed that all the ALL blast cells, bone marrow and peripheral cells during the two aplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that AA and ALL can represent evolution of the same abnormal clone.
Adolescent↗
Peripheral blood lymphocyte subsets after allogeneic bone marrow transplantation: reconstitution and correlation with the occurrence of acute graft-versus-host disease.
Peripheral blood lymphocyte subsets were enumerated at regular intervals during the first year after allogeneic bone marrow transplantation (BMT) in 21 Chinese patients. Eight of these patients had acute graft-versus-host disease (GVHD) while they were assessed at the time of engraftment. Our results show in patients receiving allogeneic BMT: (1) T and NK cells were the predominant lymphocyte subsets in the early reconstitution stage while B cells were severely depleted; (2) absolute numbers of the major lymphocyte subsets normalised in 4-5 months; (3) an increased percentage of T cells that expressed the activation antigen HLA-DR and a reversed CD4:CD8 ratio were observed throughout the first 12 months after BMT; (4) patients with acute GVHD had significantly higher white cell count and NK cell percentage than those not complicated by acute GVHD.
Acute Disease↗
An unrelated marrow donor registry in Hong Kong.
One of the limitations of allogeneic bone marrow transplant is the availability of HLA-compatible donors. HLA-identical or one antigen mismatched related donors can only be found for up to 40% of adult and 25% of paediatric patients in Hong Kong requiring a marrow transplant. The rest must rely on donors identified from volunteer unrelated marrow donor panels. Almost all our patients are Chinese but most volunteers in the worldwide marrow donor registries are Caucasians whose HLA profiles are different. Thus an unrelated marrow donor registry for Chinese was established in Hong Kong in 1991 and > 17,000 volunteers have participated. More than 300 local and overseas Chinese patients have so far been referred to our Registry for donor search. Suitable donors have been found ultimately for 40% of them. So far, 26 marrow transplants have been performed using unrelated donors from this registry. They include six overseas Chinese patients.
Asian People↗
Bone marrow transplantation in Hong Kong.
Comprehensive programmes for BMT started in Hong Kong in 1990. As of September 1993, there are a total of 13 BMT beds in Government-funded University Hospitals performing about 110 transplants per year or 18 transplants per million population per year. So far, 194 transplants were performed: allogeneic BMT (72.2%), autologous BMT (11.8%), matched unrelated donor BMT (8.8%), identical twin BMT (1.5%), mismatched BMT (2.1%) and second BMT (3.6%). The major indication was haematological malignancy (84%). About 40% of the patients were prepared by chemotherapy alone. A combination of CsA and short MTX was the commonest GVHD prophylaxis. The incidence of GVHD was the same as in the Caucasians. Results of transplant outcome were comparable to those reported by the International Bone Marrow Transplant Registry.
Bone Marrow Transplantation↗
Poor outcome of intensive chemotherapy for adult acute lymphoblastic leukemia: a possible dose effect.
Fifty consecutive adult patients with acute lymphoblastic leukemia (ALL) were treated with an intensive cyclical chemotherapy and the mean received dose of individual cytotoxic drug was retrospectively studied. The median age was 28 years. Twenty-one (43%) had white blood cell (WBC) count over 30 x 10(9)/l. Of the 26 patients with successful cytogenetic studies, ten (28%) had unfavorable clonal chromosomal abnormalities (four Philadelphia chromosome, six others). A high complete remission (CR) rate (86%) was achieved. This was associated with delivery of 100% of the planned dosage of vincristine, prednisone, and daunorubicin at induction. Dose reduction of asparaginase, the fourth drug in the induction protocol, was recorded in 20 (40%) patients. The CR rate of these patients was not adversely affected. Dose reduction was recorded during consolidation (38 of 43 remitters) and maintenance (18 of 20 remitters) as a result of treatment toxicity. The mean received dose of teniposide, Ara-C, asparaginase, mercaptopurine, and methotrexate was 73% (SD 7%), 73% (SD 7%), 62% (SD 41%), 65% (SD 15%) and 73% (SD 17%) of the planned dosage, respectively. The 5-year overall survival and leukemia-free survival (LFS) were 11% (95% CI: 0-27%) and 13% (95% CI: 0-26%), respectively. Even standard-risk patients had 4-year LFS of only 26% (95% CI: 0-57%). Among 36 remitters not withdrawn from consolidation, there were 29 treatment failures after a median follow-up of 42 months; 25 (86%) of these were leukemia relapse, three (10%) were toxic death during consolidation, and one patient (4%) died from therapy-related myelodysplastic syndrome. We postulate inadequate drug delivery during postremission therapy contributed to the high relapse rate in the whole group as well as the standard-risk patients.
Adult↗
Toxic occupational exposures and paroxysmal nocturnal haemoglobinuria.
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Benzene↗
Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification.
Seminested polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity-determining region 3 of the immunoglobulin (Ig) gene heavy chain from the malignant cell specimens of patients with leukemias and lymphomas of B-cell lineage. Two different pairs of primers were used sequentially. Twenty of the 27 (74%) acute lymphoblastic leukemia (ALL) patients, 14 of 19 (74%) chronic lymphocytic leukemia (CLL) patients and eight of 20 (40%) non-Hodgkin's lymphoma (NHL) patients, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by the seminested PCR. False-negative results appeared to occur more commonly in cases of lymphoma. The PCR analysis was also less likely to be positive if one-stage PCR studies with either pair of primers were both negative. The seminested PCR technique was found to have a high sensitivity of detecting malignant cells at the level of 0.02%. The clinical application of this assay needs to be investigated further.
Base Sequence↗
False non-paternity in a family for prenatal diagnosis of beta-thalassaemia.
Initial screening for the common beta-thalassaemia mutations with allele-specific oligonucleotide probes in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified beta gene, was a codon 43 nonsense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for beta-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this 'artefact' of false non-paternity is worth noting.
Adult↗
Pulmonary toxicity in patients with non-Hodgkin's lymphoma treated with bleomycin-containing combination chemotherapy.
Subclinical and clinical bleomycin-induced pulmonary toxicity (BIP) were investigated retrospectively in 109 patients with non-Hodgkin's lymphoma treated by combination chemotherapy containing bleomycin. A decrease in carbon monoxide diffusing capacity (DLCO) was found in 12.8% of patients. The cumulative risk of abnormal DLCO increased with the increasing total cumulative dose of bleomycin. No significant difference in the rate of BIP was observed between patients receiving bleomycin/Adriamycin/cyclophosphamide/vincristine/prednisone (BACOP; bleomycin given at 10 mg/m2 for 4 weeks) and bleomycin/Adriamycin/cyclophosphamide/vincristine/dexamethasone/methotre xate/ folinic acid (m-BACOD; bleomycin given at 4 mg/m2 for 3 weeks, methotrexate given at 200 mg/m2. Monitoring for subclinical BIP should be considered in patients with non-Hodgkin's lymphoma even if only a low dose of bleomycin was given in the presence of other chemotherapeutic agents.
Adolescent↗
Primary posterior chamber IOL implantation in penetrating ocular trauma.
This paper describes the experience of primary cataract extraction and posterior chamber IOL implantation in 11 eyes with penetrating ocular trauma. The primary surgical procedure consisted of repair of corneoscleral laceration, cataract extraction, posterior chamber IOL implantation and in certain cases, removal of intraocular foreign body and vitrectomy. 10 out of 11 cases had a post operative visual acuity of 6/18 or better, with 9 out of 11 having a post operative visual acuity of 6/12 or better. One case initially had a visual acuity of 6/24 but later developed retinal detachment with a visual acuity of 'hand movements'. Another patient developed a small localised retinal detachment during the tenth postoperative month but with successful surgery, attained a visual acuity of 6/6. The encouraging results suggest that this procedure may be recommended in carefully selected cases, under the management of an experienced surgeon.
Adult↗
Prenatal quantitation of number of X-chromosomes by slot blot hybridization and autoradiography.
OBJECTIVE: To study the use of slot blot hybridization as a method of prenatal quantification of the number of X-chromosomes in chorionic villi samples. METHOD: DNA of chorionic villi from fetuses with karyotypes of 46,XY; 45,XO; 47,XXX; 69,XXX and 48,XXXX were extracted, slot blotted and hybridized to the following radioactive probes: beta 0.9, FVIII, pY3.4 and pBLUR. DNA of chorionic villi from five other fetuses with unknown karyotypes were similarly blotted and hybridized. Autoradiography with pre-exposed films was carried out and the density of each of the hybridized bands was scanned by a laser densitometer. RESULTS: It was found that with increasing amounts of DNA in the samples, the intensity of the bands hybridized with FVIII and beta 0.9 probes increased proportionately. However, the intensity of the bands obtained with the probes pY3.4 and pBLUR (probes containing multiple repeat sequences) varied little with increasing DNA concentrations. The ratios of radioactivity obtained for the two probes FVIII/beta 0.9, were well correlated with the number of X-chromosomes in the samples. Calculations of the FVIII/beta 0.9 ratio for the five samples with the unknown karyotypes gave a correct prediction of the number of X-chromosomes in each case. CONCLUSION: Slot blot hybridization can be used as a method of prenatal quantitation of the number of X-chromosomes in chorionic villi samples. The method could be useful for rapid prenatal diagnosis of other numerical chromosomal abnormalities.
Adult↗
Effective salvage therapy using all-trans retinoic acid for relapsed and resistant acute promyelocytic leukemia.
All-trans retinoic acid (ATRA) has been shown to be active against acute promyelocytic leukemia (APL). Six patients with APL, either in relapse or resistant to initial chemotherapy were reinduced with ATRA 100 g/m2/day for 6 weeks. Complete remission was achieved in all six of them. Side effects were seen in two of them. ATRA appears to provide a relatively safe and reliable means to induce a complete remission in patients with refractory or relapsed APL.
Adolescent↗
Bronchogenic carcinoma in young patients at risk for acquired immunodeficiency syndrome.
Several case reports have suggested that bronchogenic carcinoma occurs more frequently in young patients who are human immunodeficiency virus (HIV) seropositive. We investigated the incidence of bronchogenic carcinoma and its clinical presentations in young patients at risk for HIV infection. The tumor registry of Bellevue Hospital was reviewed, and 261 cases of bronchogenic carcinoma during the period from 1976 to 1979 (pre-AIDS period) and 232 during the period from 1987 to 1990 (AIDS period) were identified. These cases were stratified into age groups: 45 or younger, 46 to 55, 56 to 65, and 66 years or older. All patients aged 45 years or younger in the AIDS period were subdivided by HIV risk, and clinical characteristics were compared among the subgroups. Results revealed no increased incidence of bronchogenic carcinoma from the pre-AIDS period compared with the AIDS period. These results suggest that HIV seropositivity is not a risk factor for bronchogenic carcinoma.
Acquired Immunodeficiency Syndrome↗
Three year results of radial keratotomy surgery at the National University Hospital, Singapore.
This paper presents the three year results of radial keratotomy (RK) surgery on 51 of the first 59 consecutive eyes at the National University Hospital in Singapore. Before surgery, uncorrected visual acuity was worse than 6/24 in all eyes with 33.3% worse than 6/60. The average pre-operative spherical equivalent (SE) was -4.56 Dioptres(D). Three years after surgery the mean SE was -0.66D, a change of 3.9D; and 72.5% of eyes were within 1D of emmetropia. 70.6% had uncorrected visual acuity of at least 6/12 with no eyes having worse than 6/60 visual acuity. Analysis based on levels of pre-operative myopia showed that the best visual and refractive results were obtained in patients with SE of -6D or less. None of the patients were troubled by complications such as glare, fluctuating vision, irritation and discomfort three years after surgery. Our results indicate that RK surgery is safe and effective through the three years and more following surgery.
Adult↗
Excimer laser photorefractive keratectomy in Singapore--a new treatment modality for myopia.
BACKGROUND: Myopia is a national epidemic in Singapore. Photorefractive Keratectomy (PRK) for the treatment of myopia using the Argon Fluoride Excimer Laser commenced in January 1992 at the Singapore National Eye Centre. METHODS: An open, prospective, non randomised clinical trial to assess the efficacy, predictability, stability, and safety of PRK for the correction of myopia between -2.0 to -6.0 dioptres. RESULTS: One hundred and fifty-five eyes of one hundred and thirty-five patients underwent PRK between January and September 1992, of which thirty-one had completed at least six months of follow-up. Twenty-nine of the thirty-one patients (93.5%) achieved an unaided visual acuity of at least 6/12. Twenty-six patients (83.9%) were within 1 dioptre of emmetropia. There was an initial over-correction in all patients which regressed to a plateau at around three or four months. Corneal haze did not pose a significant problem. Three patients had ocular hypertension, and another developed a mild allergic reaction to the antibiotic-steroid ointment. CONCLUSIONS: Excimer Laser Photorefractive Keratectomy is a very effective, fairly predictable, stable and safe surgical method for the treatment of myopia.
Adult↗
Bone marrow transplantation for thalassemia in Hong Kong: the early experience.
The first experience of bone marrow transplantation (BMT) for thalassemia in Hong Kong is reported. Of the three children transplanted using a matched allogeneic donor, two have been surviving disease free 291 and 256 days post-BMT respectively. The other child rejected the graft and remained transfusion dependent. Mild graft versus host disease occurred in one of the children which subsided on cyclosporin A alone. The regimen-related toxicities were mild and easily manageable. Thus the result is encouraging and the procedure is now accepted as an option of treatment for good risk patients in Hong Kong.
Bone Marrow Transplantation↗