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Biomedical subjects

H P Lin

Publications and source records attributed to H P Lin.

At least 19 recordsLinked to original sources
PubMed2005

Secondary B-cell acute lymphoblastic leukemia following Wilms' tumor: clinical and in vitro chemosensitivity studies.

We report the clinical features and in vitro chemosensitivity assay findings of a 13-year-old girl who developed secondary B-cell acute lymphoblastic leukemia (ALL) 7 years after a diagnosis of Wilms' tumor. The patient was treated using the Berlin - Frankfurt - Muenster (BFM) ALL chemotherapy protocol with poor response to initial therapy before succumbing to sepsis. An in vitro chemosensitivity assay on her peripheral blood lymphoblasts was performed while she was undergoing induction therapy and showed a high level of resistance to drugs commonly used for ALL therapy, e.g. steroids, anthracyclines, vincristine and L-asparaginase. The mechanism of chemoresistance was not elicited, but was probably not related to P-glycoprotein (P-gp) over-expression. We believe that the in vitro chemosensitivity assay is a good indicator of cellular response to chemotherapy and may provide reliable information for the basis of the selection of drugs to be used for the treatment of similarly rare patients rather than relying on "standard" protocols.

Adolescent↗
PubMed2005

Haemophagocytic lymphohistiocytosis in Malaysian children.

OBJECTIVES: To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre. METHODS: All patients diagnosed with HLH between 1998 and 2004 were studied. Clinico-pathological data of these patients were prospectively collected and analysed. RESULTS: Thirteen consecutive patients (eight boys) with a median age of 28 months were seen. All patients presented with high-grade unremitting fever and almost all, with hepatosplenomegaly and cytopenias. Neurological manifestations, which ranged from irritability to seizures and coma, were seen in 10 (77%) patients. Other common presenting features include liver dysfunction (46%) and skin rash (38%). All patients were treated using the HLH-94 protocol chemotherapy which consisted of a combination of etoposide, dexamethasone and cyclosporine. Complete response was seen in seven patients while two required bone marrow transplantation and one developed secondary acute myeloid leukaemia. Two patients died before treatment could be commenced. Overall mortality rate in our series was 46%. CONCLUSIONS: Haemophagocytic lymphohistiocytosis is an uncommon disease with a high fatality rate. Due to its protean clinical manifestations, it may be underdiagnosed. Early detection and prompt institution of appropriate therapy is necessary to improve the outcome in affected patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Treating childhood acute myeloid leukaemia with the AML-BFM-83 protocol: experience in a developing country.

Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.

Adolescent↗
PubMed2002

Surveillance study of bacteraemic episodes in febrile neutropenic children.

We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.

Adolescent↗
PubMed2002

Enzyme replacement therapy for Gaucher Disease: the only experience in Malaysia.

Gaucher Disease may now be treated with enzyme replacement therapy (ERT) or bone marrow transplantation (BMT). Both have their advantages and disadvantages. Results with BMT are curative when successful but limited by the scarcity of an appropriate donor. ERT offers very good relief of symptoms but treatment is lifelong and cost of treatment exorbitant. Patients in developing countries are particularly disadvantaged and management remains a dilemma for both doctor and patient.

Child↗
PubMed2001

Specific binding of the C-terminal Src homology 2 domain of the p85alpha subunit of phosphoinositide 3-kinase to phosphatidylinositol 3,4,5-trisphosphate. Localization and engineering of the phosphoinositide-binding motif.

Phosphoinositide second messengers, generated from the action of phosphoinositide 3-kinase (PI3K), mediate an array of signaling pathways through the membrane recruitment and activation of downstream effector proteins. Although pleckstrin domains of many target proteins have been shown to bind phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and/or phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) with high affinity, published data concerning the phosphoinositide binding specificity of Src homology 2 (SH2) domains remain conflicting. Using three independent assays, we demonstrated that the C-terminal (CT-)SH2 domain, but not the N-terminal SH2 domain, on the PI3K p85alpha subunit displayed discriminative affinity for PIP(3). However, the binding affinity diminished precipitously when the acyl chain of PIP(3) was shortened. In addition, evidence suggests that the charge density on the phosphoinositol ring represents a key factor in determining the phosphoinositide binding specificity of the CT-SH2 domain. In light of the largely shared structural features between PIP(3) and PI(4,5)P(2), we hypothesized that the PIP(3)-binding site on the CT-SH2 domain encompassed a sequence that recognized PI(4,5)P(2). Based on a consensus PI(4,5)P(2)-binding sequence (KXXXXXKXKK; K denotes Arg, Lys, and His), we proposed the sequence (18)RNKAENLLRGKR(29) as the PIP(3)-binding site. This binding motif was verified by using a synthetic peptide and site-directed mutagenesis. More importantly, neutral substitution of flanking Arg(18) and Arg(29) resulted in a switch of ligand specificity of the CT-SH2 domain to PI(4,5)P(2) and PI(3,4)P(2), respectively. Together with computer modeling, these mutagenesis data suggest a pseudosymmetrical relationship in the recognition of the phosphoinositol head group at the binding motif.

Amino Acid Sequence↗
PubMed2001

Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer.

OBJECTIVE: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin. METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out. RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable. CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.

Adolescent↗
PubMed2001

Acquired immunodeficiency syndrome presenting as childhood non-Hodgkin's lymphoma.

Two children with non-Hodgkin's lymphoma (NHL) as the presenting illness of acquired immunodeficiency syndrome (AIDS) are described. There was a delay in diagnosing the underlying AIDS in both cases. In the first case, an 18-month-old boy with stage IV, high-grade,T-cell NHL, the diagnosis of underlying AIDS was suspected only when he developed recurrent and profound opportunistic infection during chemotherapy. The second case, an eight-month-old female infant presented initially with hepatosplenomegaly and thrombocytopenia of undetermined cause. She had progressive abdominal distension and swelling of her right eye one year later due to high grade B-cell NHL. She was later found to be sero-positive for HIV during pre-chemotherapy screening. As the prevalence of HIV infection continues to increase, HIV infection should be considered in the differential diagnoses of childhood hepatosplenomegaly and thrombocytopenia, and as a possible underlying cause of childhood cancer, especially NHL.

Fatal Outcome↗
PubMed2001

Providing a cure for beta thalassaemia major.

The current treatment options for beta thalassaemia major patients include conservative treatment with blood cell transfusions and iron chelation or stem cell transplantation. Regular blood transfusions inevitably lead to multi-organ haemosiderosis and are attended by risks of blood-borne infections. Results from stem cell transplantation are good and suggest that this should be offered as first line therapy when a matched sibling donor is available because the patient is often cured and able to live a normal life. Of 38 Malaysian children who underwent bone marrow or cord blood transplantations using matched sibling donors, 29 (76%) are now cured.

Adolescent↗
PubMed2001

Infantile myofibromatosis.

Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with widespread visceral involvement. It is characterised by its unique ability to spontaneously regress and has a typical histological appearance of actin-positive fibroblasts arranged in whorls or fascicles and vessels in a pericytomatous pattern. A male infant with multiple lesions involving the subcutaneous tissue and bone from birth is described and followed-up for two years. Treatment of IMF is dependent on the location of the tumour/s with surgery or chemotherapy reserved for rapidly progressive or symptomatic disease. However, due to the low rate of recurrence and the possibility of spontaneous tumoral regression, therapeutic abstention, as practised in our patient, is justified.

Humans↗
PubMed2000

Characterization of a strain-specific monoclonal antibody to hepatitis delta virus antigen.

Sequences of the hepatitis delta virus (HDV) vary to different degrees among isolates. A monoclonal antibody, designated as HP6A1, against the antigen of HDV (HDAg) has been characterized for its specificity. HP6A1 bound to HDAg of isolate 25 (genotype I) that was used for immunization, but not to others of both genotypes I and II. The epitope recognized by HP6A1 was then determined by a phage library displaying various heptapeptides. A consensus peptide deduced has the best match with that of residues 4-10 of HDAg (isolate 25). To confirm the phage mapping result, Escherichia coli recombinant proteins containing different lengths and various segments of HDAg (isolate 25) were constructed. The shortest HDAg segment contained in the fusion protein that reacted with HP6A1 was residues 1-10. When this peptide was added to the N-terminus of a heterologous protein engineered for eucaryotic expression, the fusion protein was detected by HP6A1. It is concluded that HP6A1 recognizes an epitope located at the N-terminus of HDAg (isolate 25). Since viruses of quasi-species exist in natural infections, a question of how different viral strains interact in vivo remains to be explored. The highly specific MAb opens a possibility to examine the fate of one strain in the presence of other related species in a cell transfection system.

Amino Acid Sequence↗
PubMed2000

Clinical features and treatment outcome of children with myeloid antigen coexpression in B-lineage acute lymphoblastic leukemia: a study of 151 Malaysian children.

The purpose of the study was to evaluate the incidence of myeloid antigen coexpression and its prognostic significance in childhood acute lymphoblastic leukemia (ALL) in Malaysia. A retrospective study was conducted of all ALL cases (< or = 12 years old) diagnosed and treated in University Hospital, Kuala Lumpur, Malaysia between 1 January 1992 and 30 May 1995, with available immunophenotype data. Presenting features and treatment outcome of 39 B-lineage ALL patients with myeloid antigen coexpression (My+B) were compared with 112 B-lineage ALL patients without myeloid antigen coexpression (My-B) for similarity in demographic, clinical and laboratory features and their treatment outcome. My+B and My-B patients were treated with a uniform treatment protocol. Myeloid antigen coexpression was defined as more than 30% isolated leukemic cells positive for CD13 and/or CD33. The ages at diagnoses ranged from 2 months to 12 years. Median age was 4 years. The incidence of myeloid antigen coexpression was 23 per cent. Univariate analyses showed that presenting features were similar between My+B and My-B with regard to age, sex, race, FAB morphology, white cell count, hemoglobin level, platelet count, liver/spleen size, central nervous system or mediastinal involvement, presence of lymphadenopathy, and proportion of blast cells detected in the marrow. Treatment outcome were not significant between the two groups. The 2-year event free survival was achieved in 44 per cent of My+B and 57 per cent of My-B (p = 0.11). The 2-year overall survival rates were 62 per cent for My+B vs. 77 per cent for My-B (p = 0.08). This study demonstrates that myeloid antigen coexpression is fairly common and constitutes 23 per cent of childhood ALL within the Malaysian population and that it is not an adverse risk factor in childhood ALL.

Antigen Presentation↗
PubMed2000

Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol.

The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.

Age Factors↗