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Biomedical subjects

S L Tien

Publications and source records attributed to S L Tien.

At least 19 recordsLinked to original sources

The incidence and patterns of BCR/ABL rearrangements in chronic myeloid leukaemia (CML) using fluorescence in situ hybridisation (FISH).

INTRODUCTION: Chronic myeloid leukaemia (CML) is characterised by the formation of the BCR/ABL fusion gene, usually as a result of the Philadelphia (Ph) translocation between chromosomes 9 and 22. MATERIALS AND METHODS: The incidence of both typical and atypical BCR/ ABL gene rearrangements was determined in 110 patients suspected of CML using dual fusion fluorescence in situ hybridisation (DF-FISH) probes. RESULTS: Eighty-seven per cent of CML patients showed Ph translocation while 13% were negative for the Ph chromosome. About 71.9% of Ph-positive patients displayed the typical DF-FISH signal pattern. Atypical patterns among the Ph-positive patients included the concurrent loss of residual proximal 9q and distal 22q (10.4%), complex translocation with additional partners (9.4%), supernumerary Ph (3.1%), loss of residual 9q sequences proximal to breakpoint (3.1%), and deletion of distal derivative 22q signal (2.1%). Cryptic genetic alterations with loss of proximal 9q sequences were found in 13.5% of CML Ph-positive patients, which is associated with poor prognosis. Fusion signals were detected in 57.1% of CML Ph-negative patients, indicating cryptic BCR/ABL rearrangements (i.e., masked Ph). CONCLUSION: FISH is able to detect BCR/ABL fusion in CML with masked or variant Ph not apparent with conventional karyotyping. Establishment of signal patterns with FISH is important as atypical patterns may have clinical prognostic implications.

Gene Rearrangement↗

The importance of high resolution chromosome analysis in the diagnosis of birth defects: case reports of holoproscencephaly and cystic hygroma.

INTRODUCTION: The goal of cytogenetics is the detection of chromosomal abnormalities, achieved by the analysis of adequate numbers of metaphases at the appropriate bands per haploid set (BPHS). CLINICAL PICTURE: Two cases presented here include a foetal blood sample (FBS) of a 33-week-old referred with holoproscencephaly by ultrasonography, and an amniotic fluid (AF) specimen of a 14-week-old foetus with cystic hygroma, cardiac and renal defects. OUTCOME: The FBS had a deletion at 18p11.31. Another laboratory had earlier given a normal cytogenetic result on its AF sample. In the second case, an unbalanced 46,XY,der(5)ins(5;3) (q33.1;q26.2q27)mat karyotype was obtained with the AF sample. In both cases, the abnormalities were more obvious when band levels were > or =450 BPHS. CONCLUSION: This report underscores the importance of obtaining longer chromosome preparations above the current recommended 400 BPHS for prenatal specimens. This is particularly important in cases with abnormal ultrasound findings suggestive of an underlying chromosomal pathology.

Adult↗

Radionuclide synovectomy and chronic haemophilic synovitis in Asians: a retrospective study.

Radionuclide synovectomy has been identified as the procedure of choice in treating chronic haemophilic synovitis among Caucasian populations. Its effectiveness among East Asians has not been studied. A retrospective study was carried out on 12 Asian haemophiliacs who underwent 12 radionuclide synovectomies. The average follow-up was 30.7 months (range 6-55) for primary procedures. 32P chromic phosphate and 188Re-tin colloid were injected into target joints according to protocol. There was a significant 80% decrease in the median frequency of haemarthrosis from 1.4 per month (range 0.2-7.0) to 0.25 per month (range 0.0-1.8) (P<0.05). Half of the patients had excellent results by 1 year of synovectomy. The median factor usage for target joint haemarthrosis postsynovectomy was 792 units per month (range 0-3209) reduced significantly from a presynovectomy level of 1452 units per month (range 306-7125) (P<0.05). Patients also reported a reduction in joint pain scores, and an improvement in joint mobility and quality of life. The majority of patients were satisfied with the overall outcome of radionuclide synovectomy. Radionuclide synovectomy appears to be effective in reducing the incidence of target joint haemarthrosis and quantity of factor usage for such bleeds among Asians with haemophilic synovitis.

Adolescent↗

Four pregnancies in two patients with essential thrombocythaemia--a case report.

INTRODUCTION: We report our experience of 4 pregnancies in 2 patients who had essential thrombocythaemia (ET). CLINICAL PICTURE: Two patients with ET were managed with a variety of therapeutic approaches including the use of low-dose aspirin, plateletpheresis, hydroxyurea and alpha-interferon in the course of their 4 pregnancies. TREATMENT AND OUTCOME: One patient had 2 successful pregnancies despite having platelet counts in excess of 1000 x 10(9)/L antenatally. The second patient had an intrauterine fetal death during the third trimester of her first pregnancy but had a successful second pregnancy. CONCLUSION AND CLINICAL IMPLICATIONS: Management of ET in pregnancy is still very much individualized. The impact of various treatment modalities on the pregnancy outcome remains to be proven but a favourable pregnancy outcome is possible.

Adult↗

An evaluation of point-of-care instrument for monitoring anticoagulation level in adult cardiac patients.

INTRODUCTION: Rapid point-of-care measurement of anticoagulation has become feasible with the advent of new portable devices and offers the potential for home monitoring. This study evaluates the accuracy and feasibility of such a point-of-care device, the ProTime analyser as compared with standard laboratory method (IL MCL2) for monitoring the International Normalised Ratio (INR) level in cardiac patients on oral anticoagulation therapy. MATERIALS AND METHODS: Fifty patients were studied. The majority were male (86% versus 14%). Chinese accounted for 37(74%) whereas Malay and Indian, constituted 9(18%) and 4(8%) respectively. The mean age was 55 +/- 12 years. Prosthetic heart valve replacement (46%) and atrial fibrillation (38%) were among the main indications for anticoagulation. The mean dosage of warfarin was 3.0 +/- 1.5 mg (range 1.0 to 6.5 mg) and the INR results ranged from 0.83 to 4.69 (based on the hospital laboratory method). Fingerstick and venous blood samples were collected from every patient and subjected to analysis by ProTime and IL MCL2 analysers. RESULTS: There was a good correlation of INRs between ProTime venous and IL MCL2 venous, ProTime fingerstick and IL MCL2 venous and ProTime venous and ProTime fingerstick samplings, with correlation coefficients (r) of 0.9248, 0.9403 and 0.9557, respectively. The Bland-Altman plot also showed a good correlation between the methods used without any systematic bias (limits of agreement ranged from -0.422 to +0.606 INR units on average). CONCLUSION: This rapid point-of-care device appears to have an acceptable level of accuracy for measuring INR values in the recommended target ranges in adult cardiac patients on oral anticoagulation therapy.

Adult↗

Activated protein C resistance: a study among 60 thromboembolic patients in the Singapore population.

Resistance to activated protein C (APC-R) is the commonest inherited cause of thrombosis among Caucasians. Few studies have been carried out on its prevalence in Asians. We conducted a prospective study on 60 patients with thromboembolism to determine its prevalence in our local population. The Factor V Leiden (VaQ506) mutation associated with this condition was detected by amplification of the Factor V gene by polymerase chain reaction (PCR) and digestion of the fragment with Mnl I. Three patients were found to be heterozygous for this mutation. None of the 3 patients had other concomitant hypercoagulable states. In addition, we studied the prevalence of this condition in Malays which was found to be 0.5%. Our study suggests that the incidence of APC-R is much lower here compared to the West.

Activated Protein C Resistance↗

A case report of adult T-cell leukaemia/lymphoma (ATLL).

Adult T-cell leukaemia/lymphoma (ATLL) is a unique disease with distinct manifestations, a characteristic phenotype and a likely retroviral aetiology. It is unusual in Southeast Asia, though more commonly seen in some countries like Japan. We report a case of this disease in a 71-year-old man in Singapore who presented with papular erythematous eruptions for 6 years and subsequently developed generalised lymphadenopathy. He was diagnosed to have ATLL and, despite an initial response, became resistant to combination chemotherapy. We discuss the aetiology, characteristics and management of this interesting disease.

Aged↗

Highly complex chromosomal rearrangement of chromosome 9 in a case of chronic myeloid leukemia.

A 63-year-old man with chronic myeloid leukemia (CML) was found to have a new complex Philadelphia translocation. All of the bone marrow cells had a rearrangement of a five-way translocation, t(9;22;10;12;1), involving a single chromosome 9. The patient went into blast crisis two years after initial diagnosis and the karyotype remained unchanged. He died in blast crisis 10 months later. We believe this case is a unique 5-way translocation in which four chromosomes were translocated to a single chromosome.

Chromosomes, Human, Pair 1↗

Haemophagocytosis in bone marrow aspirate--a review of the clinical course of 10 cases.

The clinical course of 10 cases where marrow aspirate showed features of haemophagocytosis was reviewed. Eight of these had a fulminant clinical course characterized by high fever, constitutional symptoms, wasting, hepatosplenomegaly with liver dysfunction, sometimes lymphadenopathy, progressive pancytopenia and coagulopathy, like that described as 'malignant histiocytosis' in the past. The remaining 2 cases did not have this classical clinical syndrome. Among the former 8 cases, 4 of them had high-grade lymphoma, 3 of whom were confirmed to be peripheral T cell lymphoma. Three of the remaining 4 had suspicious lymphomatous infiltrate on marrow trephine. In every case an extensive search for viral etiology by serology was negative. The 2 cases which did not have fulminant clinical feature were found to have lymphoma of the diffuse large cell and Ki-1 anaplastic type, respectively. A review of the literature reveal that most cases with haemophagocytic syndrome have a fulminant clinical course and are peripheral T cell lymphoma, which generally has a poor prognosis. In our study, the 8 cases with the classical haemophagocytic syndrome had a median survival of 24 days and a long-term survival of 37.5% at 28 months. Prompt initiation of chemotherapy is a life-saving measure and the only chance of achieving a long-term survival in patients with haemophagocytic syndrome if the underlying lymphoma can be diagnosed early.

Adolescent↗

Detection of protein C or protein S deficiency in patients on warfarin therapy--a study of nine patients.

This review studied 9 cases of young or middle-aged patients with protein C or protein S deficiency presenting with thrombotic events in the venous or arterial system. The clinical features were consistent with those described in the literature. Affected family members with similarly low levels were also detected in family studies, some of whom did not have any thrombotic history. Serial measurement of protein C, factor II and factor X at various International Normalization Ratio (INR) levels showed a correlation between suppression of these vitamin K dependent factors and degree of anticoagulation. Furthermore, there was a distinguishable difference in these indices (protein C level, protein C: factor II, protein C: factor X ratio) in warfarinized protein C deficient patients when compared with warfarinized patients who were not protein C deficient. This provides a means in diagnosing protein C deficiency even in warfarinized patients. Such a pattern was not found for protein S deficient patients, which may be due to the assay method used.

Adult↗

Use of low molecular weight heparin in the treatment of venous thrombosis in a patient with anti-thrombin III deficiency: a case report.

This paper describes the use of a low molecular weight heparin (LMWH) in the treatment of a thrombotic episode in a patient with anti-thrombin III deficiency. Subcutaneous Fraxiparine, a low molecular weight heparin, was successfully used in the initial treatment of a second thrombotic episode in this patient with good results--no clot extension and an almost complete resolution of pulmonary emboli. This case demonstrates the advantages of using LMWH over conventional unfractionated heparin (UFH) which include ease of administration and the rapid achievement of optimal anticoagulation in conjunction with a diminished need for laboratory monitoring.

Adult↗

Altered immunity in haemophiliacs treated exclusively with cryoprecipitate.

Sixty-five patients with haemophilia A from Singapore General Hospital, treated within the last 15 years exclusively with cryoprecipitate, were studied for the effect of the total number of exposures to random blood donors on their immune system. These haemophiliacs were aged 4 to 71 years (median 24 years) and were all apparently healthy with no clinical evidence of viral infection. None of them was a homosexual or intravenous drug user. All of them tested negative for human immuno-deficiency virus antibody and hepatitis B surface antigen. Analysis of the T-lymphocyte subset population showed 20 out of 65 haemophiliacs or 30.8% had reversal of T4/T8 ratio, ie. less than 1.00. There was no significant difference in the mean age of the 20 patients with abnormal T4/T8 ratios compared with the 45 with normal T4/T8 ratios. The mean age of the former group was 23 and the latter was 25. The group with reversal of T4/T8 ratio had exposure to 827.4 +/- 137.3 (mean +/- SEM) random blood donors, which is significantly higher than 402.5 +/- 64.1 in the group with normal T4/T8 ratio (p < 0.05). The reversal of T4/T8 ratio is predominantly due to the suppression of absolute T4 cell counts, with slightly raised absolute T8 cell counts. This abnormality may be transient or permanent. Interestingly, all the six out of 65 haemophiliacs with factor VIII inhibitor did not show any reversal of T4/T8 ratio in this study.

Adolescent↗

Main causes of pre-donation deferral of prospective blood donors in the Singapore Blood Transfusion Service.

A retrospective study of the main causes of pre-donation deferral of prospective blood donors in the Singapore Blood Transfusion Service was carried out. Computerised records of all pre-donation deferrals from 1 January 1988 to 31 December 1991 were studied. A total of 278,401 pre-donation screening interviews were carried out during this period. Forty thousand one hundred and sixty-three or 14.4% of these transactions resulted in deferral of prospective blood donors either temporarily or permanently. Analysis of the deferrals showed that the top ten defined causes were: recent ingestion of medication; influenza; low haemoglobin level; a raised blood pressure; recent sexual exposure in high-risk activity; being underweight; Hepatitis B carrier status; recent history of measles, chickenpox or other infections; tattoos, ear-piercing or acupuncture in the preceding six months; and presenting for a subsequent donation too soon. To protect blood donors and recipients, stringent donor screening criteria are necessary. Modifying physical criteria could lower deferral rates but must be preceded by studies to ensure that donors do not suffer ill-effects. Increased public education on common causes of donor deferral may also lower deferral rates by allowing prospective donors to "pre-screen" themselves. However, one-to-one medical screening and appropriate counselling are still the best means for accepting or deferring blood donors in the Singapore setting.

Blood Donors↗

Apparent change of Rhesus blood group typing in a case of ulcerative colitis.

An interesting case of ulcerative colitis with an apparent change of Rhesus blood group typing is described. To our knowledge, this has not been reported before. We postulate that during the initial active phase of ulcerative colitis, an unknown D-like antigen, possibly bacterial in origin, could temporarily give rise to a Rhesus D-positive blood group typing in a patient with Rhesus D-negative blood type. Interestingly, with continuous immunosuppressive therapy for ulcerative colitis, the patient did not develop anti-D antibodies despite multiple transfusions with D-positive blood.

Adult↗