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Biomedical subjects

T K Chan

Publications and source records attributed to T K Chan.

At least 163 records · Page 9Linked to original sources

Organization of the zeta-alpha genes in Chinese.

Analysis of alpha and zeta genes in 101 healthy normals and hospitalized patients with non-haematological diseases revealed a 3% incidence of alpha thalassaemia in the local Chinese population of Hong Kong. Triple alpha genes were found in only one person while triple zeta genes were more prevalent, occurring in 13 subjects. Studies of 28 unselected patients with Hb H disease indicated a predominance of the rightward alpha gene deletion. The extent of alpha gene deletion in homozygous alpha thalassaemia 1 was at least 18.1 kb, beginning from the BamH I site 3' to the zeta 1 gene and includes the psi alpha, alpha 2 and alpha 1 genes. Nineteen of the 20 chromosomes bearing the alpha thalassaemia 1 deletion had identical zeta-intergenic hypervariable region suggesting a common origin of this mutation. The co-inheritance of alpha thalassaemia in beta thalassaemia subjects was 8%, but did not ameliorate the clinical features of those with homozygous beta thalassaemia.

China↗

Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial.

In a prospective, randomized, parallel study, two regimens of platelet-suppressant therapy (PST)--dipyridamole-aspirin and pentoxifylline-aspirin--were compared with standard oral anticoagulation with warfarin in the prevention of prosthetic heart valve thromboembolism. In the entire group of 254 patients followed for 395.6 patient-years, the thromboembolic rate was significantly less in the warfarin group (warfarin vs dipyridamole-aspirin, p less than .005; warfarin vs pentoxifylline-aspirin, p less than .05). Subgroup analysis disclosed that, in patients with isolated mitral valve replacement, warfarin was superior to both of the PSTs with respect to the prevention of thromboembolism (warfarin vs dipyridamole-aspirin, p = .005; warfarin vs pentoxifylline-aspirin, p less than .05). Furthermore, a significant number of our patients could not tolerate the antiplatelet agents. However, in the rare situation in which repeated significant bleeding occurs despite careful adjustment of the dosage of warfarin, PST may be an acceptable alternate method of thromboembolism prophylaxis.

Adult↗

Hydrops fetalis due to an unusual form of Hb H disease.

The occurrence of Hb H hydrops fetalis is reported for the first time. The mother has zeta-alpha thalassemia 1 (zeta zeta alpha alpha/----) and the father has non-deletion alpha thalassemia [zeta zeta alpha alpha/zeta zeta (alpha alpha)T]. The complete deletion of the zeta alpha cluster on one chromosome was confirmed by quantitation of alpha and zeta gene numbers, the normal alpha and zeta gene patterns arising from the remaining normal chromosome, and the decreased alpha/beta globin chain ratio of 0.57. The non-deletion alpha thalassemia defect could only be identified by the imbalanced alpha/beta globin chain ratio of 0.65 in the presence of normal gene numbers and patterns. The newborn was markedly anemic, unlike those with classical Hb H disease, because the non-deletion alpha thalassemia defect is more severe than alpha thalassemia 2. The decreased zeta genes during fetal life might have additional deleterious effects. In this family, the distinct BamHI restriction fragment length polymorphism in the hypervariable region of the zeta genes may be used for future prenatal diagnosis.

DNA Restriction Enzymes↗

BamH I polymorphism in the Chinese: its potential usefulness in prenatal diagnosis of beta thalassaemia.

The prevalence of the BamH I site 3' to the beta globin gene in Chinese people was determined in 123 normal subjects, 40 patients with heterozygous beta thalassaemia, and 25 patients with homozygous beta thalassaemia. The site was present in 71.1% and absent in 28.9% of the chromosomes carrying normal beta genes. All 25 patients with beta thalassaemia major had the site. This BamH I polymorphism may be used for prenatal diagnosis in about 29% of the pregnancies at risk.

Adult↗

Hypofibrinogenemia due to increased fibrinolysis in two patients with acute promyelocytic leukemia.

Two patients with acute promyelocytic leukemia and severe bleeding associated with hypofibrinogenemia were studied. The markedly shortened whole blood clot lysis time and dilute clot lysis time suggested that the defect was an increase in fibrinolysis. Although disseminated intravascular coagulation could not be totally excluded as an alternative mechanism, excessive fibrinolysis was confirmed as the pathogenic cause by the prompt response to the administration of tranexamic acid. The low circulating plasminogen, alpha 2 plasmin inhibitor level and the presence of alpha 2 plasmin inhibitor-protease complex in both patients suggested that the increased fibrinolysis probably resulted from the liberation of plasminogen activator from the promyelocyte.

Adult↗

Acute intravascular hemolysis due to accidental formalin intoxication during hemodialysis.

A patient accidentally exposed to formalin during hemodialysis developed acute intravascular hemolysis. In vitro study showed that formalin has direct oxidant action on red blood cells. Formalin intoxication should be recognized as a cause of acute hemolysis during hemodialysis and is not invariably fatal, provided further exposure is stopped in time and the complications prevented.

Adult↗

Cell-free synthesis of factor VIII related protein.

Polyadenylated ribonucleic acid (RNA) was isolated from confluent human endothelial cells in culture and translated in a cell-free rabbit reticulocyte lysate protein-synthesizing system. Using specific immunoprecipitation, the translation product was found to contain 1.58% VIII related protein (VIII R), which has a molecular weight of 0.26 X 10(6), similar to the subunit of VIII R present in normal plasma. This indicated that VIII R messenger RNA is responsible for the synthesis of subunits only and intracellular post-translational events are required for the assembly of tetramer and multimers.

Antigens↗

Sitosterol and cholesterol metabolism in a patient with coexisting phytosterolemia and cholestanolemia.

Sitosterol and cholesterol metabolism were studied in a patient with coexisting phytosterolemia and cholestanolemia, and in a control subject, both on similar diets containing about 170 mg cholesterol and 135 mg phytosterols per day. The turnover of 22,23-3H-sitosterol and 4-14C-cholesterol, given intravenously, were followed for up to 372 days. The specific activity-time curves for both sterols were resolved into two exponentials and fitted into a two-pool model. The half-lives of both exponential curves for sitosterol, in the patient, were abnormally long. Equilibration of the tracer between the two pools, in the patient, occurred at about 30 days as compared to 10-15 days in the control subject. The daily turnover of sitosterol in the patient was estimated to be 10 times greater than that in the control subject. The patient's total body exchangeable pool of sitosterol was 9.6 g or about 80 times the amount found in the control. The patient's plasma phytosterol levels fell by 25% when he went on a diet containing only 10 mg phytosterols per day. During this period the specific activity of his plasma sitosterol with respect to an equilibrated dose of 3H-labeled tracer remained constant; this was compatible with the absence of endogenous synthesis. Cholesterol turnover in the patient showed prolonged half-lives for both exponential curves and reduced fractional daily loss from the fast-exchanging pool. The patient's xanthoma sterols underwent 16% and 55% exchange with plasma sitosterol and cholesterol, respectively, on day 60, indicating the presence of a third exchangeable pool.

Adult↗

Acute intravascular hemolysis indicating thrombosis of Bjork-Shiley aortic prosthesis.

A patient with a Bjork-Shiley aortic prosthesis inserted two years and four months prior to receiving adequate anticoagulant therapy suddenly had severe intravascular hemolysis develop as a result of thrombosis of her aortic prosthesis. There was no notable hemodynamic compromise. The mechanism of the intravascular hemolysis is discussed.

Aortic Valve↗

The effect of oral contraceptives on coagulation and fibrinolytic parameters in the Chinese--a prospective study.

Thirty-two Chinese and 7 Caucasians were studied prospectively for 12 months for the effects of oral contraceptives (OC) on certain coagulation and fibrinolytic parameters. In both ethnic groups there was an increase in alpha 1 antitrypsin level. There was no significant change in antithrombin III concentration measured either by radioimmunoassay (At-III-RIA) or chromogenic assay (anti Xa-chromogenic) in the Chinese, but a significant decrease in anti Xa-chromogenic at 7 months and At-III-RIA at 12 months in the Caucasians. Also, alpha 2 plasmin inhibitor (alpha 2 PI) levels were unchanged in the Chinese but a significant increase occurred in the Caucasians at 12 months. Enhanced fibrinolytic response to venous occlusion was demonstrated in the Chinese at 12 months but not in the Caucasians.

Adult↗

Characterization of factor VIII related protein synthesized by human endothelial cell: a study of structure and function.

Crossed immunoelectrophoresis showed that factor VIII related protein (VIII R) synthesized in the human endothelial cell (EC-VIII R) had faster electrophoretic mobility than that secreted into the culture medium (MED-VIII R). Sodium dodecyl sulphate agarose gel electrophoresis followed by radioimmunofixation showed that EC-VIII R consisted of molecules varying from 0.26 x 10(6) to 3.76 x 10(6) daltons while MED-VIII R had molecules ranging from 0.93 x 10(6) to greater than 10 x (10)6 daltons, similar to that present in plasma. The smallest VIII R molecule present in normal plasma or spent culture medium (0.93 x 10(6) daltons) corresponded to a tetramer of subunits of 0.22-0.24 x 10(6) daltons. Only molecular forms greater than 3.76 x 10(6) daltons possessed ristocetin cofactor activity. Sonication (15 mu amplitude for 30 secs) effectively broke the non-covalent bonds of the VIII R multimers resulting in smaller molecules. Thus endothelial cells in culture synthesized VIII R subunits and assembled them into the higher multimeric forms on secretion. Different types of von Willebrand disease could result from defects of either of the two processes.

Antigens↗

[Effects of gliclazide and glibenclamide on platelet function, fibrinolysis and metabolic control in diabetic patients with retinopathy (author's transl)].

In order to compare the metabolic and hemobiological properties of two sulfonylureas, thirty-five non-insulin-dependent diabetics were randomly assigned to two groups. Each group was given either gliclazide (n = 20) or glibenclamide (n = 15) for six months. Metabolic control was improved in both groups, as evidenced by the decrease in HbA1 concentrations. A significant fall in ADP (1 and 4 microM)--induced platelet aggregation was recorded in the gliclazide group, while antithrombin III levels remained normal throughout the trial and plasminogen activator levels increased. These hemobiologic changes may be effective in preventing the vascular complications of diabetes. In contrast, glibenclamide did not alter platelet aggregation. Furthermore, a significant decrease in both antithrombin III levels and basal and venostasis-stimulated plasminogen activator levels were seen in glibenclamide patients. The beneficial changes in hemostasis seen in gliclazide patients probably result from a direct effect of the drug since hemobiological parameters and metabolic control parameters were not correlated.

Blood Glucose↗

Erythrocyte hemighosts: a hallmark of severe oxidative injury in vivo.

Erythrocyte hemighosts and ghosts were found in five patients: two with severe oxidant haemolysis caused by chemicals or drugs, and three G6PD deficient subjects with haemolysis triggered by infection and/or drugs. Scanning and transmission electron-microscopy showed that the hemighost consisted of a thinned-out part with antero-posterior apposition of the membrane and a thicker spheroidal part containing most of the haemoglobin. Heinz bodies were found in both parts of the cell close to the membrane. Large number of hemighosts (30-90%) is an ominous sign as three of our five affected patients died. The removal of these cells by exchange transfusion or the induction of forced diuresis probably saved the life of the other two patients. Experiments in rabbits showed that hemighosts were found only with severe oxidative injury induced by a large dose of acetylphenylhydrazine (50 mg/kg) and the spleen was not required for their formation. The marked congestion in the splenic sinusoids and other microcirculation results from sludging of these damaged rigid cells and is an important pathophysiological mechanism in severe oxidant injury.

Adult↗

Venous thrombosis in haemoglobin H disease after splenectomy.

While venous thrombosis and pulmonary embolism are rare among the Chinese, two of nine patients with haemoglobin H disease developed these complications after splenectomy. The clinical data of the two patients were reported and the relevant literature reviewed. It was concluded that the persistent thrombocytosis and an intravascular haemolysis, particularly prominent in this form of thalassaemia, are contributory to the hypercoagulable state.

Adult↗

Antithrombin III and fibrinogen degradation product (fragment E) in diabetic nephropathy.

Plasma antithrombin III (AtIII), serum fragment E (FgE) and urine AtIII and FgE were measured in 25 diabetic patients with proteinuria above 1 g per day and compared to that in 25 patients with non-diabetic nephropathy, matched for the degree of proteinuria. Plasma AtIII concentrations were normal in both groups but FgE concentrations were increased. The level of plasma AtIII was directly related to HbA1 concentrations in the diabetics. For the same degree of proteinuria, the diabetic patients lost more AtIII and FgE in the urine. Urine AtIII was found to be mostly bound to activated procoagulants. Both urine AtIII and urine FgE correlated inversely with creatinine clearance. It was concluded that intraglomerular thrombosis probably contributes to the deteriorating renal function in diabetic nephropathy and is reflected in the concentrations of urine AtIII and FgE.

Adult↗