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Biomedical subjects

K F Wong

Publications and source records attributed to K F Wong.

At least 91 records · Page 5Linked to original sources

Operating theater blood transaction system. A "virtual" blood transfusion service that brings the blood bank to the operating table.

We describe an operating theater blood transaction system (OTBTS) that is a novel computer software system incorporating electronic crossmatch and the concept of a "self-service" blood banking system in the operating theater. Through this system, the surgeons and the anesthetists can issue blood units for intraoperative transfusion for the patients with a negative antibody screen without the need for a porter service or pneumatic tube system. Since implementation of the OTBTS, the time for obtaining compatible blood for intraoperative transfusion has been reduced from 20 to 30 minutes to around 1 minute. Furthermore, the crossmatch-transfusion ratio was reduced to 1.05. The 23% of patients who required extra blood units (i.e., more than originally anticipated) during surgery further benefited from the system. The blood stock reserved for patients undergoing surgery was reduced by 20%. Therefore, the OTBTS is a system that can greatly enhance the efficiency and safety of intraoperative transfusion and can also save workforce resources.

Blood Banks↗

Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia--is there a consistent pattern?

The group of putative natural killer cell lymphomas, also known as NK/T cell lymphomas (nasal and nasal-type) has been characterized only in recent years. Whilst a good amount of clinical information has been gathered on this group of uncommon lymphoid neoplasms, there is little information on the cytogenetic or molecular alterations. A review of the literature shows that chromosomal abnormalities are indeed commonly found in these tumours, and aberrations involving chromosome 6q are most frequent. Other non-random abnormalities include +X, i(1q), i(7q), +8, del(13q), del(17p), i(17q), and 11q23 rearrangement. It appears that deletions of the chromosome 6 at around q21-23 region is the commonest recurrent chromosomal abnormality, and fluorescence in situ hybridisation studies have confirmed the occurrence of deletions at 6q22-23 in the CD3- CD56+ tumour cells. Search for the involved genes located in this chromosome region can potentially shed light on the molecular pathogenesis of the natural killer cell neoplasms.

Chromosome Aberrations↗

Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients.

A new method, based on the ion-translocating properties of the ionophores nigericin and A23187, is described for loading large unilamellar vesicles (LUVs) with the drugs vincristine and ciprofloxacin. LUVs composed of distearoylphosphatidylcholine/cholesterol (DSPC/Chol) (55:45 mol/mol) or sphingomyelin (SPM)/Chol (55:45 mol/mol) exhibiting a transmembrane salt gradient (for example, internal solution 300 mM MnSO4 or K2SO4; external solution 300 mM sucrose) are incubated in the presence of drug and, for experiments involving divalent cations, the chelator EDTA. The addition of ionophore couples the outward movement of the entrapped cation to the inward movement of protons, thus acidifying the vesicle interior. External drugs that are weak bases can be taken up in response to this induced transmembrane pH gradient. It is shown that both nigericin and A23187 facilitate the rapid uptake of vincristine and ciprofloxacin, with entrapment levels approaching 100% and excellent retention in vitro. Following drug loading, the ionophores can be removed by gel exclusion chromatography, dialysis, or treatment with biobeads. In vitro leakage assays (addition of 50% mouse serum) and in vivo pharmacokinetic studies (in mice) reveal that the A23187/Mn2+ system exhibits superior drug retention over the nigericin/K+ system, and compares favorably with vesicles loaded by the standard DeltapH or amine methods. The unique features of this methodology and possible benefits are discussed.

Animals↗

Anomalous solubility behavior of the antibiotic ciprofloxacin encapsulated in liposomes: a 1H-NMR study.

Many drugs are weak bases and can be accumulated into liposomes in response to a pH gradient to achieve high internal drug concentrations. This study is aimed at gaining an understanding of the relationship between the retention of the fluoroquinolone antibiotic ciprofloxacin in liposomes and the intraliposomal form and location of this drug. 1H-NMR spectroscopy was used to probe the interactions experienced by ciprofloxacin following uptake into large unilamellar liposomes (LUV). It is shown that ciprofloxacin is located in the aqueous interior of the liposomes and is self-associated in the form of small stacks. It does not precipitate out of solution even though the intraliposomal ciprofloxacin concentration can exceed its solubility in aqueous solutions by almost two orders of magnitude. The results also indicate that little entrapped ciprofloxacin partitions into the inner monolayer of the LUV. As a result of the lack of precipitation and rapid exchange properties, ciprofloxacin can respond quickly to changes in electrochemical equilibria such as depletion of the pH gradient. This provides a rationale for the rapid leakage of this drug in response to serum destabilization or depletion of the pH gradient.

1,2-Dipalmitoylphosphatidylcholine↗

Splenic lymphoma with villous lymphocytes showing del(7) and inv(10).

A 49-year-old woman presented with splenic lymphoma with villous lymphocytes (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic lymphoproliferative disorders. A review of the literature on cytogenetic abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and may be important in the pathogenesis of this disorder.

Chromosome Deletion↗

De novo AML with trilineage myelodysplasia and a novel t(11;12)(p15;q13).

De novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) is an uncommon form of leukemia characterized by a dyshematopoietic picture accompanying the acute leukemia, a poor response to induction chemotherapy, and a tendency to relapse with pure myelodysplastic syndrome. Cytogenetic information on this entity is scarce, although some cases have been reported to be associated with t(7;11)(p15;p15). A 41-year-old woman who had a history of radiotherapy for breast cancer presented with AML/TMDS and was found to have a unique t(11;12)(p15;q13) abnormality.

Adult↗

Translocation(8;20;21)(q22;q13;q22) in acute myeloblastic leukemia with maturation: a variant form of t(8;21).

A 39-year-old man was diagnosed as having acute myeloblastic leukemia with maturation (AML-M2). Cytogenetic studies revealed 45,X,-Y,t(8;20)(q22;q13)[21]/46,XY[3]. Molecular analysis of the marrow mononuclear cells by reverse transcription-polymerase chain reaction with nested AML1 and ETO primers showed amplification of the AML1/ETO fusion transcript, thus confirming that the chromosomal aberration was in fact a masked t(8;21), i.e., variant t(8;20;21)(q22;q13;q22).

Adult↗

Acute myeloid leukemia with a novel (7;11)(q36;q13) translocation.

A 79-year-old female presented with acute myeloblastic leukemia without maturation. Cytogenetic studies showed a previously undescribed abnormality of t(7;11)(q36;q13). The significance of the involvement of 11q13 in the pathogenesis of myeloid leukemia is discussed.

Aged↗

Abnormal erythropoiesis in erythroleukemia: a fluorescence in situ hybridization study.

Erythroleukemia is an uncommon leukemia with heterogeneous morphologic and karyotypic features. Some cases might actually represent acute myeloid leukemia with a reactive erythroid hyperplasia. In this report, we described a 68-year-old woman with erythroleukemia and monosomy 7 and showed by fluorescence in situ hybridization that both myeloid and erythroid lineage were clonally involved and that both normal and abnormal erythroid populations coexisted, albeit indistinguishable by morphological examination. These findings may account for the variation in the erythropoietic activity observed in the clinical course of erythroleukemia.

Aged↗

Changes in morphology and behaviour of retinal growth cones before and after crossing the midline of the mouse chiasm - a confocal microscopy study.

The growth of retinal axons was investigated in different regions of the optic chiasm in C57 pigmented mouse embryos aged embryonic day 13 (E13) to E15. Individual retinal axons and their growth cones were labelled anterogradely by DiI and imaged using a confocal imaging system. In aldehyde-fixed embryos, retinal growth cones display a simple form in the optic nerve and become more complex in morphology in the chiasm. The complex form is particularly prominent in those axons that turn to the ipsilateral tract in the premidline region of chiasm. Moreover, complex growth cones are also commonly found in axons in the postmidline chiasm, which are markedly different in morphology from those axons in the premidline region, suggesting that the postmidline chiasm contains a novel environment for the pathfinding of retinal axons. In another experiment, the dynamic growth of retinal axons is studied in a brain slice preparation of the living retinofugal pathway. Retinal axons show an intermittent growth across the premidline and postmidline chiasm. Extensive remodelling of growth cone form followed by a shift in growth direction is commonly seen during the pause periods, indicating that signals that guide axon growth across the chiasm are not restricted to the midline, but are laid down throughout the chiasm. Moreover, dramatic changes in axon trajectory are noted first at the premidline chiasm where the uncrossed axons segregate from the crossed axons, and second at the postmidline chiasm where specific sorting of retinal axons according to their position in the dorsal ventral retinal axis and their ages are known to take place. These results show that there are two distinct environments, separated by the midline in the chiasm, where axons show different responses to local guidance cues and develop the distinct fibre orders.

Animals↗

Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation.

The fluoroquinolone antibiotic ciprofloxacin has been encapsulated into large unilamellar vesicles (LUV) at efficiencies approaching 100%. Drug accumulation proceeded in response to a transmembrane gradient of methylammonium sulfate and occurred concomitantly with the efflux of methylamine. A mechanism for the encapsulation process is described. LUV composed of dipalmitoylphosphatidylcholine-cholesterol (DPPC/chol), distearoylphosphatidylcholine-cholesterol (DSPC/chol), or sphingomyelin-cholesterol (SM/chol) increased the circulation lifetime of ciprofloxacin after intravenous (i.v.) administration by > 15-fold. The retention of ciprofloxacin in liposomes in the circulation decreased in the sequence SM/chol > DSPC/chol > DPPC/chol. Increased circulation lifetimes were associated with enhanced delivery of the drug to the livers, spleens, kidneys, and lungs of mice. Encapsulation of ciprofloxacin also conferred significant increases in the longevity of the drug in the plasma after intraperitoneal administration and in the lungs after intratracheal administration in comparison to free ciprofloxacin. The efficacy of a single i.v. administration of an SM/chol formulation of ciprofloxacin was measured in a Salmonella typhimurium infection model. At 20 mg of ciprofloxacin per kg of body weight, the encapsulated formulation resulted in 10(3)- to 10(4)-fold fewer viable bacteria in the livers and spleens of infected mice than was observed for animals treated with free ciprofloxacin. These results show the utility of liposomal encapsulation of ciprofloxacin in improving the pharmacokinetics, biodistribution, and antibacterial efficacy of the antibiotic. In addition, these formulations are well suited for i.v., intraperitoneal, and intratracheal or aerosol administration.

Animals↗

Association of pure red cell aplasia with T large granular lymphocyte leukaemia.

AIM: To define the relation between T large granular lymphocyte (T-LGL) leukaemia and pure red cell aplasia in Chinese patients. METHODS: Patients with T-LGL leukaemia were identified from a consecutive series of Chinese patients with chronic lymphoproliferative disorders. The diagnosis of T-LGL leukaemia was based on typical morphological and immunophenotypical features, and confirmed by the detection of clonal T cell receptor gene rearrangement. The clinicopathological features, response to treatment, and long term follow up were also examined. RESULTS: Five patients were identified as having T-LGL leukaemia from a consecutive series of 33 Chinese patients with chronic lymphoproliferative disorders. The median follow up time was 45 months. An obvious lymphocytosis was present in only two cases, although an increase in large granular lymphocytes in the peripheral blood was found in four. In one case, the LGL count was within the normal range. Epstein-Barr virus encoded early nuclear RNA was negative in all the cases. There was no evidence of rheumatoid arthritis, and none of the patients presented with recurrent infections. On follow up, pure red cell aplasia occurred at some stage of the disease in all the patients. This responded to treatment with cyclosporin A in two and with antithymocyte globulin in one. Two patients remained transfusion dependent. CONCLUSIONS: In contrast to Western patients, Chinese patients with T-LGL leukaemia do not appear to suffer from rheumatoid arthritis and recurrent infections, but pure red cell aplasia is a major cause of morbidity in this ethnic group.

Aged↗

Immunostimulation of murine spleen cells by materials associated with bovine milk protein fractions.

Purified bovine milk proteins that were added to cultures of murine spleen cells significantly increased cell proliferation and production of immunoglobulin M. Casein and a whey mixture consisting of alpha-lactalbumin, bovine serum albumin, bovine gamma globulin, and beta-lactoglobulin (beta-LG) were stimulatory. Of the three beta-LG preparations that are commercially available (beta-LG containing variants A and B, purified variant A, and purified variant B), the unseparated mixture containing both the A and B variants showed the most immunomodulatory activity. Both alkaline treatment and trypsin digestion of the beta-LG preparation markedly reduced its effectiveness. Polymyxin B, while greatly diminishing the stimulatory effect of lipopolysaccharide, had no significant effect on either the enhancement of cell proliferation or the enhancement of immunoglobulin production by beta-LG. In the presence of S-(n-butyl)-homocysteine sulfoxamine, the stimulatory effect of beta-LG on cell proliferation and IgM production in vitro was markedly reduced.

Animals↗

Hairy cell leukemia variant with t(2;8)(p12;q24) abnormality.

Hairy cell leukemia variant is an uncommon chronic B-cell lymphoproliferative disorder characterized clinically by splenomegaly and marked leukocytosis. Cytologically, the leukemic cells are distinguishable from those of classical hairy cell leukemia by the presence of single, central, and vesicular nucleoli. Cytogenetic information for this uncommon leukemia is scanty, although structural abnormalities involving 7q34 have been reported in few cases. We report a patient with hairy cell leukemia variant who has t(2;8)(p12;q34) but without [corrected] c-MYC oncogene rearrangement.

Aged↗

Low frequency of TEL/AML1 in adult acute lymphoblastic leukemia.

Translocation (12;21)(p13;q22) is a recently characterized aberration in acute lymphoblastic leukemia, and results in the fusion of the TEL and the AML1 genes. It is the most common translocation in pediatric acute lymphoblastic leukemia (ALL), occurring in about one third of the cases. To determine the frequency of TEL/AML1 in adult ALL, we studied 4 cases of T lineage ALL and 26 cases of B lineage ALL. Only one positive case was identified, giving a very low frequency of 3.3%. In this patient, TEL/AML1 was still detectable in complete hematologic remission. The apparent age predilection of t(12;21) warrants further investigations.

Adolescent↗

Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.

Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Adolescent↗

Parvovirus B19 infection in Hong Kong.

Human parvovirus B19 is a small DNA virus that can cause a number of diseases, notably erythema infectiosum in children, and aplastic crisis in patients with chronic haemolytic disorders. With the availability of serological tests for parvovirus infection, much is known about the prevalence of this virus in the Western population. However, there have not been any data on the epidemiological pattern of parvovirus B19 infection in Hong Kong and its surrounding region. In this report we have studied the sero-prevalence of parvovirus B19 in Hong Kong in 1983 and 1993, and were able to show a low incidence of parvovirus infection in the intervening 10 years, leading to a shift in the prevalence rate of parvovirus infection in the general population. From 1991 to 1996, of 276 patients presenting with illness which might have been caused by B19, only 2.5% were positive for IgM and 19.6% for IgG anti-B19. The prevalence of IgG anti-B19 among patients with thalassaemia major requiring frequent blood transfusion in 1995 was similar to those in the same age group in the general population, substantiating the observation that B19 infection was not common in Hong Kong in recent years.

Adolescent↗

Biclonal B-cell chronic lymphocytic leukemia with inv(14)(q11q32).

Cytogenetic biclonality is a rare occurrence in chronic lymphocytic leukemia. A 59-year-old man was diagnosed to have B-cell chronic lymphocytic leukemia with typical morphology and immunophenotype (CD5+, CD19+, and CD23+). However, karyotypic analysis of the small lymphocytes showed the presence of two distinct unrelated clones, including one with inv(14).

Aged↗