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Biomedical subjects

H L Lim

Publications and source records attributed to H L Lim.

At least 19 recordsLinked to original sources
PubMed2006

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.

Adult↗
PubMed2006

A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer.

BACKGROUND: Intracellular gemcitabine triphosphate (dFdCTP) levels can be optimised by administering gemcitabine at a fixed dose rate infusion. PATIENTS AND METHODS: Patients with chemonaive advanced non-small cell lung cancer (NSCLC) were randomised to receive gemcitabine at a fixed dose rate gemcitabine 750 mg/m(2) over 75 min (arm A) or gemcitabine 1000 mg/m(2) over 30 min (arm B) on days 1 and 8 every three week cycle. Carboplatin at AUC of 5 was administered in both treatment arms on day 1 of each cycle. End points were activity, tolerability and pharmacokinetics of plasma and intracellular gemcitabine. RESULTS: 76 patients were randomised. Response rate was 34% in arm A and 42% in arm B. Toxicity and quality of life scores were similar for both treatment arms. Mean plasma Cmax(gemcitabine) and mean dFdCTP AUC in arm A was 20.8 microM +/- 17.2 microM and 35,079 +/- 18,216 microM*min respectively and in arm B, 41.2 +/- 13.9 microM and 32 249 +/- 11 267 microM*min respectively. dFdCTP saturation was reached in Arm B but not in Arm A. CONCLUSION: The saturability of dFdCTP accumulation in Arm A suggests optimal delivery of gemcitabine is achieved using fixed rate infusion compared to 30-min infusion. Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC. However, this entails a longer infusion time with associated higher costs involved.

Adult↗
PubMed2000

Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer.

Docetaxel has a response rate of greater than 30% in first-line treatment of Western patients with advanced non-small cell lung cancer (NSCLC). The goal of this open-label. phase II study was to evaluate the activity and safety profile of docetaxel in Asian patients with inoperable untreated stage III NSCLC. Docetaxel was given at 100 mg/m2 as a 1-h infusion every 3 weeks. Prophylactic dexamethasone was given to reduce hypersensitivity reactions and edema. Thirty-five patients were enrolled in the study. The response rate was 34% (95% CI, 19%-50%) according to intent-to-treat analysis. No complete response was observed. Twenty-four patients (69%) had grade 3 or 4 neutropenia in cycle 1, and febrile neutropenia was seen in 12 patients. Six patients (17%) experienced mild fluid retention. Docetaxel is an active agent in first-line treatment of Asian patients with locally advanced NSCLC, with the main toxicity being neutropenia. Fluid retention was a minor problem in this study.

Adult↗
PubMed2000

Immunoglobulin D multiple myeloma in our hospital--a rare occurrence.

Immunoglobulin (Ig) D multiple myeloma is a rare presentation, usually with an aggressive course and a poorer prognosis. It accounts for about 1-2% of newly diagnosed mulitple myeloma patients. Due to its rarity, reports on Ig D multiple myeloma are limited in the literature. We therefore present 4 cases of Ig D multiple myeloma in our hospital over a period of 8 years between 1990 to 1998. The average age of presentation of our patients was 44 years old with a female preponderance. Common presenting symptoms were appetite and weight loss and bone pain. Two patients presented with neurological symptoms and 2 with renal impairment. Three patients had an associated lambda paraproteinaemia and the fourth had a kappa paraproteinaemia. A common finding in Ig D myeloma is a small or no spike seen on serum electrophoresis together with heavy Bence Jones proteinuria. A review of the literature on Ig D myeloma is also presented.

Adult↗
PubMed1998

L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.

A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a large left parieto-occipital haemorrhage 7 days after completion of induction chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L-asparaginase. The haemorrhage could not be attributed to thrombocytopenia, disseminated intravascular coagulopathy, arterio-venous malformation, berry aneurysm or leukaemic infiltration because each of these causes was carefully investigated into and excluded. We conclude that the intracranial haemorrhage was likely L-asparaginase induced, an uncommon but recognised complication associated with L-asparaginase therapy.

Adult↗
PubMed1997

Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus infection.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the host's immunomodulatory response to infective agents. To evaluate the TNF-alpha system in patients with chronic hepatitis C virus (HCV) infection, plasma, serum, and peripheral blood mononuclear cells (PBMC) were prospectively collected from 53 patients and 33 healthy control subjects. Circulating TNF-alpha and TNF receptors were assayed by their respective enzyme immunoassays. In addition, TNF-alpha mRNA was quantitated in PBMC using a branched DNA assay, and production of TNF-alpha by PBMC with and without lipopolysaccharide was also assessed. Patients with chronic HCV infection had a higher level of circulating TNF-alpha compared to healthy control subjects (9.62 +/- 6.01 vs 3.66 +/- 1.23 pg/ml, P < 0.001). They also had higher circulating levels of TNF receptors compared to control (CD120a: 3323 +/- 1267, pg/ml, N = 49 vs 1855 +/- 422 pg/ml, N = 33, P < 0.001; CD120b: 1290 +/- 650 pg/ml, N = 51, vs 863 +/- 207 pg/ml, N = 33, P < 0.001). Plasma TNF-alpha level correlated with circulating CD120a (r = 0.52, N = 49, P < 0.001) and weakly with CD120b (r = 0.32, N = 51, P = 0.02). Plasma TNF-alpha also correlated with markers of hepatocellular injury, including ALT (r = 0.34, N = 53, P = 0.01) and alpha-GST (r = 0.31, N = 43, P = 0.042), but not with serum HCV RNA levels. There was no difference in the TNF-alpha mRNA levels in PBMC between patients with chronic HCV infection (1.4 +/- 1.9 units/10[6] cells, N = 8) and healthy control subjects (2.1 +/- 1.4 units/10[6] cells, N = 8, P = NS). There was also no difference in the spontaneous production of TNF-alpha by PBMC (1 x 10[6] cells/ml) between patients with chronic HCV infection (14.2 +/- 36.5 pg/ml, N = 11) and healthy subjects (11.9 +/- 14.0 pg/ml, N = 14, P = NS). However, patients with chronic HCV infection produced more TNF-alpha upon stimulation with lipopolysaccharide compared to healthy control subjects (1278 +/- 693 pg/ml, N = 11, vs 629 +/- 689 pg/ml, N = 14, P < 0.05). These data indicate that the TNF-alpha system is activated in patients with chronic HCV infection.

Adolescent↗
PubMed1995

alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic hepatitis C virus infection.

alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosolic concentration, and short half-life. To determine the clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV) infection, serum alpha GST levels were measured in 96 patients with chronic HCV infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA levels, and liver histology. Different methods of serum collection did not affect alpha GST values, indicating that this was a stable serum marker. In 93% of patients with chronic HCV infection, alpha GST was elevated and showed an excellent correlation with serum aminotransferases. Histologic analysis revealed a correlation of alpha GST with both lobular inflammation and bile duct lesions. There was no correlation between serum alpha GST levels and the demographic features, mode of transmission, virologic, other histologic parameters, or subsequent response to interferon-alpha. During serial monitoring in patients undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with biochemical relapse and in some patients virologic relapse in the presence of normal liver biochemistry. alpha GST was persistently elevated in all nonresponders. Four of six of those patients who responded completely followed by early relapse had elevated alpha GST intermittently or continuously during therapy despite normalization of serum aminotransferases. Two of five of those with a complete and sustained response had elevated alpha GST during treatment and follow-up, and both were also seropositive for HCV RNA during follow-up. These data demonstrate that alpha GST is a stable marker, has similar diagnostic utility as serum aminotransferases, and may have a role in the monitoring of patients undergoing interferon-alpha therapy.

Adult↗
PubMed1995

Plasma glutathione concentration in patients with chronic hepatitis C virus infection.

It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-alpha (IFN-alpha) therapy in chronic hepatitis C virus (HC) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 27 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.27 +/- 0.12 micrograms ml-1, HCV 1.62 +/- 0.11 micrograms ml-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 +/- 0.007 U ml-1, HCV 0.230 +/- 0.007 U ml-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.

Adult↗
PubMed1995

Treatment of acute promyelocytic leukaemia in first relapse with all-trans retinoic acid.

A 27-year-old Chinese woman with acute promyelocytic leukaemia in first relapse after the initial conventional induction chemotherapy 18 months earlier was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2 and subsequently increased to 65 mg/m2 on day 15. Complete remission was achieved after a total of 40 days of ATRA alone. Serial marrow examinations during induction showed progressive maturation of myelopoiesis without bone marrow hypoplasia. There was a significant reduction in number of cells with the t(15;17) translocation when complete remission was achieved. ATRA was very well-tolerated. The symptoms of dry skin and intermittent headache were self-limiting.

Adult↗
PubMed1994

Cholestatic hepatitis leading to hepatic failure in a patient with organ-transmitted hepatitis C virus infection.

A 51-year-old heart transplant recipient who developed subfulminant hepatic failure because of organ-transmitted hepatitis C virus (HCV) infection is described. He presented with a predominantly cholestatic liver damage after heart transplantation. An extensive evaluation, including abdominal ultrasound and computed tomography scan and endoscopic retrograde cholangiopancreatography was unrevealing. Liver biopsy, however, was suggestive of a large duct obstruction with prominent portal and pericellular fibrosis, marked cholestasis, pericholangitis with marked ductular proliferation, and diffuse hepatocyte degeneration. Antibody to HCV (anti-HCV) was initially negative. He deteriorated in the ensuing 3 months. A repeat enzyme immunoassay-2 test for anti-HCV 4 months after initial presentation was weakly positive. Quantitation of serum HCV RNA by branched DNA assay revealed high level viremia, 547 x 10(6) genome equivalents per milliliter. Using in situ polymerase chain reaction, HCV RNA was detected in the cytoplasm in > 80% of the hepatocytes. The patient underwent interferon alfa therapy, and serum HCV RNA levels were reduced 20-fold after four doses. Unfortunately, the patient developed pulmonary aspergillosis and died. This case illustrates that in immunosuppressed patients anti-HCV is not a good marker for the diagnosis of HCV infection, and HCV can cause a progressive form of cholestatic liver disease mimicking a large duct obstruction.

Base Sequence↗
PubMed1994

Therapy for chronic hepatitis C.

Hepatitis C is the silent epidemic of the 1970s and 1980s. Interferon alfa is currently the only effective treatment. Enthusiasm for interferon therapy must be tempered because advanced disease usually requires years or even decades to develop and does not occur in all patients. Few patients with chronic hepatitis C derive long-term improvement from a single 6-month course of interferon therapy. Most initial responders relapse and require long-term interferon treatment to suppress the virus. Obviously, the initial goals and expectations for interferon therapy require rethinking. Therapy should not be undertaken by physician or patient with the idea that therapy will be limited to 6 months. The most appropriate goal of therapy now appears to be the long-term control of the biochemical, virologic, and histologic activity of the disease. Unfortunately, the most effective therapeutic regimen for achieving this goal is not yet known and will require continued clinical research.

Chronic Disease↗
PubMed1994

Multiple myeloma: the National University Hospital (NUH) experience.

The aim of this retrospective study was to define the characteristics of local patients with multiple myeloma. Twenty-nine de novo cases were accrued from October 1986 to January 1992 at the National University Hospital of Singapore. Features like median age of presentation, sex distribution, the incidence of IgG, IgA and light chain subtypes were similar to published data. However IgD myeloma appeared to be more common here and it tended to be more advanced at presentation. Objective response rate to treatment with the melphalan-prednisolone combination was about 40% with a median survival of 18 months.

Adult↗
PubMed1993

A practical approach to the management of depression.

Depression is a common and treatable condition. Failure to diagnose it may lead to unnecessary investigations, delay in treatment and an increased risk of suicide. Anti-depressant drugs are the first line of treatment. Tricyclics are generally the drugs of choice as their efficacy is very well established. Second generation antidepressant drugs are preferred for the elderly and those with heart disease as they tend to have milder side effects and are less toxic in overdose. Electroconvulsive therapy is indicated in those with severe depression, high suicide risk or failed drug treatment. Psychotherapy is usually used as an adjunct to pharmacotherapy whilst lithium is used to prevent recurrence of depression.

Antidepressive Agents↗
PubMed1993

Hepatic infarction complicating a transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portocaval shunt (TIPS) is being used with increasing frequency to treat variceal bleeding and portal hypertension. Like any other invasive vascular procedure, it has the potential for serious complications. We report a case of a woman who underwent a TIPS procedure for variceal bleeding due to hepatitis C and sustained a hepatic infarction as a complication of the procedure. We caution about the potential for catastrophic complications with this procedure, and recommend that it be performed only in centers with a liver transplant program nearby.

Female↗