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Biomedical subjects

F Y Lau

Publications and source records attributed to F Y Lau.

At least 19 recordsLinked to original sources

Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA-haplotype: avoiding fatal transfusion-associated graft-versus-host disease while preserving anti-leukemic effect.

BACKGROUND: Fatal transfusion-associated graft-versus-host disease was observed in immunocompetent patients transfused with blood from donors homozygous for a shared haplotype with the recipient (the P-F1 barrier). We tested whether it was possible to carry out successful transplantation in a patient with relapsed acute myeloid leukemia, using peripheral blood stem cells from his HLA-homozygous brother (HLA A2, B46, DRB1 901) who shared a haplotype with the patient (HLA A2, B46,75, DRB1 901,12). METHODS: A CD34 positively selected cell fraction (5.46x 10(6) CD34 cells/kg) was infused first, followed by subsequent infusion of graded doses of donor T cells (total 7.25x10(7) T cells/kg). Nonmyeloablative chemotherapy with idarubicin and cytarabine was given during the transplantation to reduce the leukemic burden and facilitate engraftment. Polymerase chain reaction with the VNTR primers, D1S80, was used to detect engraftment. RESULTS: Complete remission (>300days) and successful donor engraftment (90%) were achieved. CONCLUSIONS: Peripheral blood stem cells transplantation from a donor with a homozygous shared haplotype is possible with a minimal preparative regimen.

Acute Disease↗

To err is human nature. Can transfusion errors due to human factors ever be eliminated?

BACKGROUND: Fatal hemolytic transfusion reaction due to ABO incompatibility occurs mainly as a result of clerical errors. Blood sample drawn from the wrong patient and labeled as another patient's specimen will not be detected by the blood bank unless there is a previous ABO grouping result. METHODS: In Hong Kong, we had designed a transfusion wristband system--portable barcode scanner system to detect such clerical errors. The system was well accepted by the house staff and had prevented two BO mismatched transfusion. Other current system of patient's identification may have similar results, but the wristband system has the advantages of being simple, inexpensive and easy to implement. The Hong Kong Government is planning to replace the personal identity card for all citizens with an electronic smart card by 2003. If the new card contains the person's detailed red cell phenotypes in digital code, then the phenotypes of all blood donors and admitted patients will be readily available. It is feasible to issue phenotype-matched blood to patients without any need of pre-transfusion testing, therefore eliminating mismatched transfusions for most patients. RESULTS: Our pilot study of 474 patients showed that the system was safe and up to 98% of admitted patients could be transfused without delays. CONCLUSIONS: Patients with rare phenotypes, visitors or illegal immigrants may still need pre-transfusion antibody screen, but if most patients can be issued blood units without testings, the potential savings in health care amount to US$14 million/year.

ABO Blood-Group System↗

Successful engraftment in two adult patients with severe aplastic anemia using nonmyeloablative conditioning followed by unrelated HLA-mismatched cord blood transplantation.

Umbilical cord blood as an alternative source of hematopoietic stem cells and nonmyeloablative conditioning are very exciting new developments in transplantation. We report here mixed chimerism in two adult patients with severe aplastic anaemia using nonmyeloablative conditioning and two-antigen mismatched cord blood transplantation resulting in satisfactory clinical response. Our results suggest that such transplant is possible with minimal toxicity.

Adolescent↗

Provision of phenotype-matched blood units: no need for pre-transfusion antibody screening.

BACKGROUND AND OBJECTIVES: The Hong Kong government is planning to introduce an electronic smart identity card for all seven million citizens in 2003. If the smart card contains the full red cell phenotype/genotype of the individual, it may be possible to transfuse phenotype-matched blood units without pre-transfusion antibody screening. We conducted a feasibility study. DESIGN AND METHODS: Red cell phenotype was determined for 407 donor blood units and 493 patients for whom an antibody screen had been ordered. The computer program selected phenotype-matched blood from the donor stock for the patients according to actual transfusion request. For patients with a positive antibody screen, full crossmatching was carried out with the computer-selected phenotype units. The frequencies of the various red cell phenotypes in the population were calculated from Red Cross data of antigen frequencies. The probabilities of finding at least one unit of phenotype-matched blood from a 300-unit hospital stock and a 4,000-unit Red Cross stock were determined for each phenotype. Cost analysis was performed. RESULTS: Ninety-two out of 493 patients received a total of 395 blood units. The required number of phenotype-matched blood units could be found for 92 patients using a 300-unit pool and for all patients using a 4,000-unit pool. We calculated that phenotype-matched blood could be provided for more than 98% of patients without antibody screening. The total cost of the project is US$ 98 million with potential savings of US$ 14 million per year. INTERPRETATION AND CONCLUSIONS: It is feasible and cost-effective to transfuse patients with phenotype-matched blood without antibody screening using a smart card system.

Blood Group Antigens↗

Improvement in transfusion safety using a specially designed transfusion wristband.

Fatal haemolytic transfusion reaction due to ABO incompatibility occurs mainly as a result of clerical error. A blood sample drawn from the wrong patient and labelled as another patient's will not be detected by the blood bank unless there is a previous ABO grouping result. We report here the detection of such clerical error by the use of a specially designed transfusion wristband. The wristband has the following special features: (i) once attached, it cannot be removed except by cutting; (ii) it has a pocket containing a transfusion label; (iii) a unique transfusion barcode is printed on each transfusion label and the corresponding wristband simultaneously by computer technology; (iv) a transfusion label removed from the wristband after attachment to the patient has a characteristic tear-mark distinguishing it from one removed prior to attachment. The blood bank only accepted those specimens bearing the tear-marked transfusion labels. All blood units for this patient were labelled with this unique transfusion code together with the patient's details. The nurses counter-checked the transfusion code on the blood units against the transfusion code on the patient's transfusion wristband prior to transfusion. If the blood sample for compatibility testing was drawn from the 'wrong' patient, the intended patient either did not carry a wristband or the transfusion codes did not match at all. Pretransfusion compatibility tests were performed on 2189 patient samples using this procedure. It was well accepted by both ward and blood bank staff. Two potential mismatched transfusions were avoided. These two clerical errors would not have been detected because neither patient had previous ABO grouping results.

Blood Banks↗

Comparison of late results of balloon valvotomy in mitral stenosis with versus without mitral regurgitation.

Balloon mitral valvotomy (BMV) is safe and effective in patients with mitral stenosis (MS) and coexisting mild mitral regurgitation (MR). Influence of preexisting MR on late outcome of BMV is under evaluation. We included 77 patients without MR and 72 with MR in this study, and compared their immediate and late results in a mean follow-up of 33 +/- 24 months after BMV. Patients with coexisting MR were older and more frequently had significant valvular calcium and atrial fibrillation than patients without MR. After BMV, mitral valve gradient decreased, and cardiac output and mitral valve area by planimetry increased significantly (all p = 0.0001) in both groups. There was no difference in values of mitral valve gradient and cardiac output after BMV between the groups. Mitral valve area was significantly smaller in patients with preexisting MR. During follow-up, there were 11 patients (14%) in the group without MR and 24 (33%) in the group with MR developed cardiac events (p = 0.006). Cumulative event-free survival was 90% at the second year, 87% at the fourth year, and 69% at the sixth year, respectively, in the group without MR versus 78%, 62%, and 37%, respectively, in the group with MR (p = 0.0014). Cox regression showed that preexisting MR was a significant predictor for late cardiac events with a threefold increased hazard risk (p = 0.0025), but age, valvular calcium, echocardiographic score, and cardiac rhythm also played a culpable role. We conclude that preexisting MR is an important risk factor for poor, late outcome of BMV.

Adolescent↗

Lack of structural rearrangement in c-kit and stem cell factor genes in Hong Kong Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia.

Stem cell factor is a haemopoietic growth factor that interacts with the c-kit-encoded transmembrane tyrosine kinase receptor during signal transduction in haemopoietic progenitor stem cells. We have screened 127 Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia for structural rearrangements in the stem cell factor and c-kit genes using Southern blot analysis. No structural rearrangements were detected in any of the bone marrow samples that were tested. It seems that structural rearrangements in the stem cell factor and c-kit genes are rare in Hong Kong patients who have a haematological malignancy.

Journal Article↗

Low frequency of c-kit expression and detection of an aberrant Kit message among Hong Kong Chinese myelogenous leukaemia patients.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It is expressed by the primitive CD34 positive haemopoietic stem cells and interacts with the Kit ligand for signal transduction. It was reported to be expressed in over 80% of acute myelogenous leukaemia (AML) patients in North America and Japan. We analyzed 20 AML patients for c-kit expression using either Northern blot analysis or flow cytometry with the YB5.B8 anti-c-kit antibodies. Only 6 out of 20 AML patients expressed the c-kit mRNA or protein product. However, a previously unreported abnormal sized 1.7-1.9 kb transcript was detected in the blast cells of 1 AML patient, 1 acute mixed lineage leukaemia patient and 1 chronic myelogenous leukaemia (CML) patient in myeloblastic transformation. Our data suggested that in most Hong Kong Chinese AML patients, leukaemia transformation may have occurred at a c-kit negative stage. Alternatively, the abnormal sized c-kit transcript that was detected in some Chinese myeloid leukaemia patients may represent an aberrant c-kit receptor that plays an important role in leukaemogenesis.

Blotting, Southern↗

A novel prognostic scoring system to predict late outcome after percutaneous balloon valvotomy in patients with severe mitral stenosis.

We developed a prognostic scoring system to predict the outcome of follow-up after balloon mitral valvotomy. The system incorporates seven variables before valvotomy: age, New York Heart Association class, fluoroscopic calcification, echocardiographic score, cardiac rhythm, mitral regurgitation, and mitral valve area. Each variable was coded with either 0 or 1 and a total score was between 0 and 7. The study included 150 patients with a mean follow-up of 33 +/- 24 months. In patients with scores of 0-1, 2-3, 4-5, and 6-7, the estimated cardiac event-free survival rate was 97%, 94%, 86%, and 68%, respectively, at 1 year; 95%, 88%, 74%, and 47%, respectively, at 3 years; and 92%, 82%, 61%, and 30%, respectively, 5 years after valvotomy (p = 0.0001). The hazard risk ratio for cardiac events was 1.7 times greater for every step up of the score (p = 0.0001). Our scoring system provides a simple but effective method to predict late outcome of balloon mitral valvotomy.

Catheterization↗

Immediate and late outcome of percutaneous balloon mitral valvotomy in patients with significantly calcified valves.

We assessed immediate and late outcome in 55 patients with significantly calcified valves (group 1) after balloon mitral valvotomy and compared the results with those from 60 patients with noncalcified or minimally calcified valves (group 2). After valvotomy, mitral valve area increased from 1.03 +/- 0.30 cm2 to 1.64 +/- 0.35 cm2 (p = 0.0001) by echo planimetry in group 1 but was significantly smaller than the mitral valve area in group 2 after valvotomy (1.94 +/- 0.38 cm2; p = 0.0001). At a mean follow-up period of 30 months (range 2 to 81 months), 51% of patients in group 1 and 83% in group 2 were symptom free (p = 0.0002). In group 2, 15 (27%) patients and in group 2, 4 (7%) patients had cardiac events (p = 0.003). The risk ratio for cardiac events was 4.3 times greater in group 1 than in group 2. In group 1, the risk ratio for cardiac events was 3.2 times higher in patients age > or = 65 years and in patients with atrial fibrillation. The 6-year cumulative cardiac event-free survival rate was 64% in group 1 and 90% in group 2 (p = 0.005). In 75 (65%) patients who had follow-up echocardiographic study (35 in group 1 and 40 in group 2), mitral valve area decreased to 1.48 +/- 0.42 cm2 at follow-up in group 1 (p < 0.01) and to 1.77 +/- 0.50 cm2 in group 2 (p = 0.3). Restenosis occurred in 16 (46%) of 35 patients in group 1 and 10 (25%) of 40 in group 2 (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of late outcome between Inoue balloon and double-balloon techniques for percutaneous mitral valvotomy in a matched study.

The follow-up results between Inoue balloon (n = 43, group 1) and double-balloon (n = 43, group 2) mitral valvotomies were compared in a patient-to-patient matched study. Matching was based on patients' age, mitral valve echo score, fluoroscopic calcification, mitral valve area before valvotomy, and follow-up period. The mean follow-up period was 13 +/- 9 months for both groups. At follow-up, 72% of patients were symptom free in each group; 2 (4.7%) patients in group 1 and 1 (2.3%) patient in group 2 underwent mitral valve replacement surgery. Of these 3 patients, 2 died after surgery, 1 from each group. The mitral valve area by Doppler was 1.8 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.4 cm2 in group 2 (p = 0.7); the area by echo planimetry was 1.7 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.3 cm2 in group 2 (p = 0.3) at follow-up. Restenosis occurred in 5 (12%) patients from each group. The cumulative restenosis-free rate was 96% at 1 years, 78% at 2 years, and 58% at 3 years in group 1 and 98%, 76%, and 51%, respectively, in group 2 (p = 0.8). Balloon selection did not appear to influence the clinical outcome at follow-up. We conclude that both the inoue balloon and the double-balloon valvotomies are effective therapies with comparable follow-up results for patients with mitral stenosis.

Adult↗

Thermodilution left-sided cardiac output for valve area determination after balloon mitral valvotomy.

This study was conducted to establish the validity of left-sided cardiac output measurement with a Swan-Ganz catheter and assess its accuracy in estimating mitral valve area (MVA) by the Gorlin formula. The use of right-sided cardiac output after balloon mitral valvotomy (BMV) can give inaccurate measurements for Gorlin-derived MVA because of the atrial septal defect (ASD) created during the procedure. The left-sided cardiac output was measured with a Swan-Ganz catheter (proximal port in the left atrium and then in the left ventricle, and distal port in the ascending aorta) in 10 consecutive patients before and after BMV. Gorlin-derived MVA cardiac output by this method was compared with (1) Gorlin-derived MVA by means of right-sided cardiac output with and without balloon occlusion of the ASD and (2) MVA measured by echocardiography. Before BMV, a close agreement with a good correlation between left-sided and right-sided cardiac output was found (r = 0.83, p = 0.006). Furthermore, Gorlin-derived MVA by cardiac output with either method was comparable with valve area by echo. After BMV, left-sided cardiac output correlated well (r = 0.92, p = 0.0002) and was comparable with right-sided cardiac output with occlusion of the ASD (mean difference 0.17 +/- 0.49 L/min, p = 0.3) but was significantly lower than the value obtained with open ASD (mean difference 0.93 +/- 0.77 L/min, p = 0.004). Comparison of the correspondent MVAs yielded similar results. Gorlin-derived MVA with left-sided cardiac output and MVA by echo were also similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗