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Biomedical subjects

L H Lee

Publications and source records attributed to L H Lee.

At least 19 recordsLinked to original sources
PubMed2006

Treatment and outcome of acquired haemophilia A with a standard conventional regimen in a cohort without associated conditions.

Acquired haemophilia A (AH) is a rare bleeding disorder with significant risk of mortality. We conducted a study on the treatment and outcomes of patients with AH diagnosed between 1998 and 2004 in our institution. Fourteen patients (age range 17-89, median 64) were followed-up from between 10-64 months (average 32 months). Inhibitor levels ranged from 5 to 450 BU. Ten patients required either recombinant activated factor VIIa or prothrombin complexes for control of bleeding. All patients received a standard immunosuppressive regimen of prednisolone 1 mg kg day(-1) and oral cyclophosphamide 50-100 mg day(-1). In addition, nine patients received intravenous immunoglobulin. Complete remission (CR) was achieved in 88% (eight of nine evaluable patients) over durations ranging from 5-78 days (average 35 days). There were three mortality; from bleeding, sepsis and cerebral infarct. Two patients were lost to follow-up. There were no relapses among patients achieving CR. Conditions associated with AH were not identified at diagnosis or subsequent follow-up in all patients. This series represent one of the largest aetiologically and treatment-wise, uniformed cohort of AH patients. Despite toxicity concerns, the combination of prednisolone and cyclophosphamide remain an effective regimen and should be among the first line of treatment choices, with careful patient selection.

Adolescent↗
PubMed2005

Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography.

BACKGROUND: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. OBJECTIVE: We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. PATIENTS/METHODS: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. RESULTS: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). CONCLUSIONS: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.

Adult↗
PubMed2003

Successful control of postsurgical bleeding by recombinant factor VIIa in a renal failure patient given low molecular weight heparin and aspirin.

An end-stage renal failure patient with lupus nephritis was treated with low molecular weight heparin (LMWH) and aspirin for cardiac ischemia. She was then subjected to surgery to recreate a new arteriovenous fistula for dialysis 1 day after discontinuing LMWH and aspirin. Severe postsurgical bleeding required wound reexploration and multiple transfusions of blood products, which nevertheless, failed to arrest bleeding. Recombinant factor VIIa (rFVIIa) as a bolus dose of 120 microg/kg successfully secured hemostasis. Bleeding in this patient was attributed to the accumulation of low molecular weight heparin activity from poor renal clearance as well as the antiplatelet activity of aspirin. The potential of rFVIIa in securing hemostasis for excessive bleeding after use of these agents is promising.

Adult↗
PubMed2002

Evaluation on the use of a portable unit versus the laboratory for the monitoring of International Normalized Ratio (INR) in orally anticoagulated patients.

INTRODUCTION: Measuring the International Normalized Ratio (INR) through a laboratory requires venipuncture and takes about 1 hour for results to be available. A portable monitor (CoaguChek Plus System), which measures the INR using fingerstick samples, is evaluated in this study to determine its clinical significance in anticoagulated and non-anticoagulated individuals. The hospital's outpatient and inpatient laboratories were also compared in the study. MATERIALS AND METHODS: Paired venous and capillary blood INRs were performed on anticoagulated patients using the monitor and the Singapore General Hospital (SGH) outpatient and inpatient laboratories (OPS and IPS labs). Paired INRs of control samples were also performed using the monitor and the IPS lab. RESULTS: We plotted the difference in INR by the 2 methods (monitor and OPS lab, n = 91) against their mean, and calculated the limits of agreement (95% of the difference would lie between -0.90 to 0.70). After a logarithmic transformation on the data, we found that for 95% of the cases, the OPS lab would differ from the monitor by 13% below to 14% above. There was also a marginal difference (95% limits of agreement of -0.14 to 0.10) when we compared the INR obtained from OPS and IPS laboratories (n = 43). Our control sample (n = 19) showed that the 95% confidence interval for the bias was -0.04 to 0.10. CONCLUSION: The monitor should be used with caution in patients with INR > 3. We suggest use of the monitor in situations where the non-anticoagulated state of a patient needs to be measured. There is a difference in INR measured by laboratories within the same institution.

Anticoagulants↗
PubMed2002

Case report on recombinant coagulation factor VIIa in the treatment of three haemophilia A patients with inhibitors in Singapore.

INTRODUCTION: We report the first experiences with use of recombinant coagulation Factor VIIa (rFVIIa) in the treatment of haemophilia A patients with inhibitors in Singapore and discuss observations in 3 patients. CLINICAL PICTURE: Case 1 bled on two separate occasions into his neck muscles and vocal cord. Case 2 had gross haematuria from bleeding in the renal calyxes. Case 3 bled into the parotid muscles. TREATMENT: rFVIIa in doses, ranging from 50 ug/kg to 90 ug/kg, at different dosing intervals, were used. OUTCOME: Excellent responses were seen in doses of 70 and 90 ug/kg. CONCLUSIONS: rFVIIa is highly effective, both clinically and cost-wise, in the treatment of these patients.

Adult↗
PubMed2002

Clinical update on deep vein thrombosis in Singapore.

Venous thromboembolism (VTE) is thought to be a rare occurrence in Asian patients. The clinical features of VTE are elusive and the disease often unsuspected. Objective testing such as the duplex ultrasound scans and pulmonary imaging are necessary as clinical diagnosis alone is inaccurate. Fatality can occur in untreated patients not suspected of the disease as shown by our post-mortem studies. Indeed VTE is one of the leading causes of maternal mortality in Singapore. There is a rising trend in the incidence of VTE in Asia. Initial studies found an incidence of about 3 per 10,000 hospital admissions in Hong Kong and Malaysia in 1988 and 1990, respectively; rising to 8 and 15.8 per 10,000 hospital admissions in Singapore 1992 and 2000, respectively. The major risk factors for developing deep vein thrombosis (DVT) in our patients are immobilisation, surgery and malignancy. While Factor V Leiden mutation and mutation at position 20,210 in the prothrombin gene are found to be extremely rare in Chinese, the rest of the thrombophilia has not been formally studied. Studies in Singapore reported rates of 3% to 7% of DVT after general surgery, 9.7% after hip surgery and 14% after total knee replacement surgery. It is difficult to compare with studies from other centres because of differences in patient selection and diagnostic criteria. Studies in Singapore showed that the use of prophylactic low molecular weight heparin completely abolished the occurrence of DVT for patients undergoing total knee replacement and colorectal surgery without an increase in bleeding complications. In conclusion, VTE is not an uncommon problem here. Major acquired risk factors do not differ from the Caucasian populations. VTE is a preventable disease and a better understanding of its epidemiology, patient-risk factors and biological factors will allow better management of this condition.

Asian People↗
PubMed2002

Idiopathic thrombocytopenia in pregnancy.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which antiplatelet autoantibodies bind to the antigens on platelet surfaces, resulting in their destruction. It is one of the most common autoimmune disorders that physicians manage today. Although it can present itself at any age, it tends to occur in young women. Hence, it commonly affects women in the childbearing age group. It is a haematological disorder for which diagnostic and treatment strategies are not well defined. In the past decade, there have been attempts for consensus in the management of patients with ITP, resulting in practice guidelines being published. The management of pregnant patients with ITP, however, has its special problems with the added responsibility of caring for 2 lives, the mother and her fetus. The choice of drugs is limited to those without teratogenic risks to the fetus and the overall aim is to prevent haemorrhage in both mother and fetus during the antenatal and peripartum periods. There are more data now to show that invasive procedures do not necessarily reduce fetal bleeding risk and are associated with more maternal morbidities, thus favouring the trend towards more conservative management.

Adult↗
PubMed2002

New aspects of the blood coagulation cascade, anticoagulants and vein thrombosis in Asia.

PURPOSE: This review describes recent views on blood coagulation and abnormalities of its physiological control that predispose to thrombosis, suggests that venous thrombosis and pulmonary embolism are more prevalent in Asia than was previously thought, and examines recent trials of novel anticoagulants for thrombosis prevention. SOURCES: 'Medline' was used to search for publications in English or with English language abstracts. CONTENT AND CONCLUSIONS: The study of blood coagulation is basic to understanding clotting and bleeding disorders, their prevention and treatment. Tissue factor, factor Xa, and thrombin are pivotal; together with physiological controls (positive and negative feedback loops, and natural anticoagulants) that first enhance thrombin generation but then preserve vessel patency by limiting haemostatic plug formation to areas of injury. Abnormalities in these mechanisms can increase thrombosis risk (thrombophilia). The traditional impression that venous thromboembolism is rare in Asia has been reinforced by the rarity of thrombophilic genetic polymorphisms outside of European populations. Nevertheless, there is increasing evidence for an increasing prevalence of symptomatic vein thrombosis and pulmonary embolism in Asia, and that thrombosis rates in 'high risk' clinical settings among elderly patients (as after major joint surgery or a stroke) now approach levels reported from the West. This indicates the need for greater clinical awareness of these conditions. Drugs now used routinely for thrombosis prevention in the West (especially low molecular weight heparins) are effective and relatively safe. New anticoagulants were even more effective in recent trials. There is urgent need for studies in Asia that define the locally relevant benefits and hazards of the increasing range of agents now available.

Adult↗
PubMed2002

Deep vein thrombosis is not rare in Asia--the Singapore General Hospital experience.

INTRODUCTION: Venous thromboembolism (VTE) is perceived to be rare in Asia, but our recent clinical experience at Singapore General Hospital (SGH) suggests otherwise. Between 1996 and 1997, there were 388 cases of confirmed deep vein thrombosis (DVT). MATERIALS AND METHODS: All patients with symptomatic DVT confirmed by duplex ultrasound studies from January 1996 to December 1997 were retrospectively studied. Their case notes were searched for a record of predisposing risk factors. RESULTS: Ultrasound imaging indicated acute thrombosis in 320 patients (82.5%), and previous, but not acute thrombosis in 68 patients (17.5%). The overall frequency rate of acute DVTs was 15.8 per 10,000 hospital admissions. The average age of patients with acute thrombosis was 58.2 years. 9.2% of patients developed pulmonary embolism (PE). Their most frequently recorded clinical predispositions were immobilisation (67%), malignancy (33%) and recent surgery (30%). One hundred and thirty patients were tested for antithrombin, protein C or protein S deficiency, and the presence of antiphospholipid antibody and 45 (35%) were found to have at least 1 positive result. CONCLUSION: DVT is not uncommon in Singapore. Our frequency rate of acute DVT of 15.8 per 10,000 admissions is much higher than previously reported rates of 2.8 and 7.9 per 10,000 admissions in 1990 and 1992, respectively. These findings confirm the need for increased awareness of VTE in Asian populations, and support the relevance of systematic studies of thrombosis risk and prophylaxis in Asia.

Adolescent↗
PubMed2001

Monoclonal antibodies against different epitopes of nonstructural protein sigmaNS of avian reovirus S1133.

Ten monoclonal antibodies (MAbs) were prepared against the nonstructural protein sigmaNS of avian reovirus S1133. Eight of them were selected for two-way competitive binding assay after coupling with horseradish peroxidase. The results allowed the definition of three epitopes, designated A, B, and C. Blocking assay of poly(A)-Sepharose binding activity of sigmaNS with MAbs indicated that MAb recognizing epitope B was able to block poly(A) oligomer binding, suggesting that epitope B is involved in ssRNA binding of sigmaNS. An immuno-dot binding assay was used to analyze the effect of denaturation on antibody recognition of the epitopes. All MAbs bound to protein sigmaNS in its native form. After denaturation by boiling in SDS and 2-mercaptoethanol, the binding of MAbs recognizing epitopes B and C was not affected. The reactivity of MAbs recognizing epitope A was fully abolished by denaturation. These results suggest that the binding of MAbs directed against epitope A is conformation-dependent; however, the recognition by MAbs of epitopes B and C is not conformation-dependent. In addition, the results from the cross-reactivity of MAbs to heterologous avian reovirus strains suggest that the three epitopes are highly conserved among these virus strains.

Animals↗
PubMed2001

Bacterial polysaccharides as vaccines--immunity and chemical characterization.

Studies on protective immunity and biochemical characterization of bacterial capsular polysaccharides have led to significant contributions to understanding of the mechanisms of infectious diseases and development of effective vaccines. Immunity to encapsulated bacteria is related to antibody response to polysaccharide (PS) antigen, interactions with T- and B-lymphocytes, and host defense mechanisms. Meningococcal, pneumococcal and Salmonella vi PSs and Haemophilus type b PS-protein conjugate vaccines have been licensed and provided effective immunity for prevention of these bacterial infections. Capsular PSs are cell-surface polymers consisting of oligosaccharide repeating units. Many PSs are highly polar and hydrophilic and interfere with cell-to-cell interactions with phagocytes. Most pneumococcal PSs are negatively charged and possess acidic components such as D-glucuronic acid and phosphate in phosphodiester bonds. Extensive immunologic cross-reactivity has been observed among bacterial capsular PSs. In infants the antibody responses to most capsular PSs are generally poor. Enhanced immunogenicity of PS antigens can be achieved through PS-protein conjugate vaccines, immunization during a critical period of perinatal development and effective antigen delivery system.

Bacterial Infections↗
PubMed2001

Management of neurocytomas: case report and review of the literature.

The purpose of this report is to review the available literature on the presentation, pathology, and treatment of central nervous system (CNS) neurocytomas. A case report of an extraventricular neurocytoma is presented along with a comprehensive literature search of patients with a diagnosis of CNS neurocytoma. CNS neurocytomas are rare neoplasms, with fewer than 240 cases reported in the literature. The majority of neurocytomas are found in the ventricular system of the brain. Immunohistochemistry is frequently used to help distinguish this tumor from other CNS neoplasms. MIB-1 proliferation index is commonly used in an attempt to predict biologic behavior. Little is known about the management of patients with this tumor, because most reports are from the pathologic literature and contain sparse information regarding clinical management. Neurocytomas are rare CNS tumors with varied biologic behavior. MIB-1 index may help direct adjuvant therapy. An excellent prognosis can be expected if a gross total resection is achieved. Postoperative radiation therapy (RT) may be considered after subtotal resection. Otherwise, RT is an option for medically inoperable or recurrent disease.

Aged↗
PubMed2001

Topical bactrim versus trimethoprim and sulfonamide against nocardia keratitis.

PURPOSE: The conventional treatment of Nocardia keratitis is with topical sulfonamides. Recently, topical trimethoprim and sulfamethoxazole (Bactrim) has been suggested as treatment. This study compares the in vitro efficacy against Nocardia asteroides of Bactrim and various ratios of trimethoprim and a sulfonamide. METHODS: Antibiotic disks were soaked with various ratios of trimethoprim and sulfacetamide sodium. They contained trimethoprim alone, sulfacetamide sodium alone, and both trimethoprim and sulfacetamide sodium at ratios of 1:40, 1:20, and 1:5. Disks containing Bactrim were also prepared. Each disk was placed on blood agar plates streaked with N. asteroides. The plates were incubated at 37 degrees C for 72 hours and then examined. RESULTS: Trimethoprim alone showed minimal effect. Sulfacetamide sodium alone had a clearance zone of 12 mm. The plates of trimethoprim and sulfacetamide sodium at ratios of 1:40, 1:20, and 1:5 had clearance zones of 14 mm, 17 mm, and 27 mm, respectively. Bactrim had a clearance zone of 70 mm. CONCLUSION: Trimethoprim or sulfacetamide sodium alone is not as effective as both drugs together. As the ratio of the two drugs was changed, potency differed against Nocardia organisms. Bactrim was the most effective antibiotic against Nocardia organisms. It should be the recommended agent for the treatment of Nocardia keratitis.

Administration, Topical↗
PubMed2000

Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii.

Expression screening of a Pneumocystis carinii-infected mouse lung cDNA library with specific monoclonal antibodies (mAbs) led to the identification of a P. carinii cDNA with extensive homology to subtilisin-like proteases, particularly fungal kexins and mammalian prohormone convertases. The 3.1 kb cDNA contains a single open reading frame encoding 1011 amino acids. Structural similarities to fungal kexins in the deduced primary amino acid sequence include a putative proenzyme domain delineated by a consensus autocatalytic cleavage site (Arg-Glu-Lys-Arg), conserved Asp, His, Asn and Ser residues in the putative catalytic domain, a hydrophobic transmembrane spanning domain, and a carboxy-terminal cytoplasmic domain with a conserved tyrosine motif thought to be important for localization of the protease in the endoplasmic reticulum and/or Golgi apparatus. Based on these structural similarities and the classification of P. carinii as a fungus, the protease was named KEX1. Southern blotting of mouse P. carinii chromosomes localized kex1 to a single chromosome of approximately 610 kb. Southern blotting of restriction enzyme digests of genomic DNA from P. carinii-infected mouse lung demonstrated that kex1 is a single copy gene. The function of kexins in other fungi suggests that KEX1 may be involved in the post-translational processing and maturation of other P. carinii proteins.

Amino Acid Sequence↗
PubMed2000

Self-assembly of the infectious bursal disease virus capsid protein, rVP2, expressed in insect cells and purification of immunogenic chimeric rVP2H particles by immobilized metal-ion affinity chromatography.

A gene encoding a structural protein (VP2) of a local strain (P3009) of infectious bursal disease virus (IBDV) was cloned and expressed using the baculovirus expression system to develop a subunit vaccine against IBDV infection in Taiwan. The expressed rVP2 proteins formed particles of approximately 20-30 nm in diameter. Those particles were partially purified employing sucrose density gradient ultracentrifugation, and the purified particles were recognized by a monoclonal antibody against the VP2 protein of IBDV P3009. To facilitate the purification of the particles, the VP2 protein was engineered to incorporate a metal ion binding site (His)(6 )at its C-terminus. The chimeric rVP2H proteins also formed particles, which could be affinity-purified in one step with immobilized metal ions (Ni(2+)). Particle formation was confirmed by direct observation under the electron microscope. The production level of rVP2H protein was determined to be 20 mg/L in a batch culture of Hi-5 cells by quantifying the concentration of the purified proteins. The chicken protection assay was performed to evaluate the immunogenicity of the rVP2H protein. When susceptible chickens were inoculated with the recombinant rVP2H proteins (40 microg/bird), virus-neutralizing antibodies were induced, thereby conferring a high level of protection against the challenge of a very virulent strain of IBDV. In conclusion, the most significant finding in this work is that both of the expressed rVP2 and rVP2H proteins can form a particulate structure capable of inducing a strong immunological response in a vaccinated chicken.

Animals↗
PubMed2000

Synthesis in Escherichia coli of avian reovirus core protein varsigmaA and its dsRNA-binding activity.

The genome segment S2 of p6ian reovirus (ARV) S1133 was cloned and sequenced. The entire S2 nucleotide sequence is 1325 bp long with one long open reading frame that encodes a protein of 415 amino acids, corresponding to varsigmaA, a major core protein of ARV. S2 possesses a pentanucleotide, TCATC, at the 3'-terminus of its plus strand, common to other known genome segments of ARV and to 10 genome segments of mammalian reovirus. Amino acid sequence analysis revealed that varsigmaA contains a carboxy-terminal region (one-fourth of the protein) that is formed from alpha-helices and beta-turns, and the remainder (three-fourths of the protein) is formed predominantly from beta-strands and beta-turns. Analysis of binding activity to poly(rI)-poly(rC)-agarose suggested that ARV protein A present in total virus-infected chicken embryo fibroblasts (CEF) had dsRNA-binding activity. To further characterize the binding activity, protein varsigmaA was subsequently expressed in Escherichia coli BL21(DE3) cells as a fusion protein and isolated by metal chelate affinity chromatography. The expressed protein evarsigmaA was further purified through a Superdex 75 HR 10/30 column after digestion of the purified fusion peptide with enterokinase. The expressed protein evarsigmaA has the same molecular weight as virion protein varsigmaA purified from ARV-infected CEF and is indistinguishable from virion protein varsigmaA by immunoblot analysis. The evarsigmaA binds cooperatively alpha (32)P-labeled dsRNA probe produced by run-off transcription of clone pGEM-3Zf(+)S4. The binding reaction is blocked by homologous ARV dsRNA or heterologous infectious bursal disease virus dsRNA and poly(rI)-poly(rC), but not by salmon sperm DNA. The results indicate that the expressed protein evarsigmaA has dsRNA-binding activity similar to that of varsigmaA obtained from infected cells, and its binding is sequence-independent.

Amino Acid Sequence↗
PubMed2000

Fewer symptoms occur in same-serotype recurrent streptococcal tonsillopharyngitis.

BACKGROUND: Most patients with acute rheumatic fever report no antecedent pharyngitis. OBJECTIVE: To determine the clinical and microbiological characteristics of recurrent group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. DESIGN: Prospective randomized trial. SUBJECTS: Symptoms were recorded and throat cultures were obtained at 4 to 6, 18 to 21, and 32 to 35 days following the start of treatment. A subset of 60 patients with subsequent GABHS episodes occurring were evaluated for a 0.2-or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer to confirm a bona fide recurrence. RESULTS: Sixteen (27%) of 60 patients had recurrent GABHS tonsillopharyngitis of the same serotype that occurred 21 days or longer following the onset of the initial GABHS infection and was associated with a 0.2- or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer, indicating bona fide recurrent infection; these recurrences all occurred within 55 days. Fewer patients with recurrent GABHS pharyngitis of the same serotype had headache (P =.02), sore throat (P =.006), fever (P =. 008), pharyngeal erythema (P<.001), pharyngeal edema (P<.001), pharyngeal exudate (P =.04), and adenitis (P =.03) compared with the initial episode. Chills, stomachache, scarlatina, tonsillar enlargement, and palatal petechiae were similar for both episodes. CONCLUSIONS: Fewer symptoms occur during recurrent GABHS pharyngitis of the same serotype compared with the initial infection. These patients may be less likely to seek physician attention, yet their infections put them at risk for sequelae.

Adolescent↗