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H Lau

Publications and source records attributed to H Lau.

At least 55 records · Page 3Linked to original sources
PubMed2001

Efficacies of lipophilic inhibitors of dihydrofolate reductase against parasitic protozoa.

Competitive inhibitors of dihydrofolate reductase (DHFR) are used in chemotherapy or prophylaxis of many microbial pathogens, including the eukaryotic parasites Plasmodium falciparum and Toxoplasma gondii. Unfortunately, point mutations in the DHFR gene can confer resistance to inhibitors specific to these pathogens. We have developed a rapid system for testing inhibitors of DHFRs from a variety of parasites. We replaced the DHFR gene from the budding yeast Saccharomyces cerevisiae with the DHFR-coding region from humans, P. falciparum, T. gondii, Pneumocystis carinii, and bovine or human-derived Cryptosporidium parvum. We studied 84 dicyclic and tricyclic 2,4-diaminopyrimidine derivatives in this heterologous system and identified those most effective against the DHFR enzymes from each of the pathogens. Among these compounds, six tetrahydroquinazolines were effective inhibitors of every strain tested, but they also inhibited the human DHFR and were not selective for the parasites. However, two quinazolines and four tetrahydroquinazolines were both potent and selective inhibitors of the P. falciparum DHFR. These compounds show promise for development as antimalarial drugs.

Alleles↗
PubMed2001

Long-term prognosis of femoropopliteal bypass: an analysis of 349 consecutive revascularizations.

BACKGROUND: Femoropopliteal bypass is the commonest procedure for lower limb revascularization. The aim of the present study was to determine the long-term outcomes of femoropopliteal bypass and evaluate the prognostic significance of various clinical factors on the long-term results. METHODS: From 1976 to 1998, 349 consecutive primary femoropopliteal bypass operations were performed on 314 patients at the University of Hong Kong Medical Centre. Indications for operation included claudication (n = 85) and limb-threatening ischaemia (n = 264). Univariate and multivariate analyses of 14 clinical variables were undertaken to identify significant prognostic factors affecting the graft patency, limb salvage and patient survival rates. RESULTS: The overall primary patency rates of femoropopliteal bypass were 88%, 79% and 76% at 1, 3 and 5 years, respectively. Type of graft material and age of patient were independent prognostic factors of graft patency. The cumulative limb salvage rates were 90%, 86% and 86% at 1, 3 and 5 years, respectively. No clinical factor was found to be predictive of ultimate limb loss. The overall survival rates were 89%, 85% and 78% at 1, 3 and 5 years, respectively. Coronary artery disease was the main cause of late death. Gender and indication for operation were the significant predictive factors of long-term survival. CONCLUSIONS: Femoropopliteal bypass using reversed long saphenous vein provided the most durable long-term patency. Autologous saphenous vein should be the choice of vascular conduit if available. Male gender and limb-threatening ischaemia were associated with a poor survival.

Aged↗
PubMed2001

Carotid artery aneurysm secondary to cystic medial necrosis.

Carotid artery aneurysm secondary to cystic medial necrosis is a rare clinical entity. We report a 59-year-old Chinese male patient who presented with a pulsatile right neck swelling for 2 months. Partial resection of the aneurysm with primary anastomosis of the internal carotid artery was performed. Histopathological examination of the aneurysmal wall demonstrated cystic degeneration of the media with accumulation of glycosaminoglycan material, consistent with the features of cystic medial necrosis. The pathogenesis of carotid artery aneurysm secondary to cystic medial necrosis is discussed.

Aneurysm↗
PubMed2001

Laparoscopic repair of incisional hernia.

A 75-year-old man developed an incisional hernia over the upper abdomen following a wedge resection of a gastric stromal tumour in 1996. This is the first published report of a successful repair of an incisional hernia via a laparoscopic intraperitoneal on-lay technique using GORE-TEX DualMesh material in Hong Kong. Compared with conventional open repair of incisional hernia, long incisions and wound tension are avoided using the laparoscopic approach. This translates into a reduced risk of wound-related complications and facilitates recovery. In selected cases, minimally invasive surgery is a safe technique for the repair of incisional hernias.

Aged↗
PubMed2000

Patient satisfaction after ambulatory inguinal hernia repair in Hong Kong.

Ambulatory surgery was introduced to Asia in the 1990s. Acceptance of ambulatory surgery by oriental patients remains largely unknown. A telephone survey was conducted to evaluate the level of patient satisfaction following ambulatory inguinal hernia repair. A total of 157 patients (61%) completed the telephone survey. More than 90% of the respondents expressed satisfaction with regard to the pre-operative, operative and post-operative service. The majority of the respondents (>80%) preferred to undergo day surgery again in case of hernia recurrence. Our findings prove that ambulatory surgery has a high level of acceptance in Chinese patients and supports the expansion of a day surgery service in Hong Kong.

Journal Article↗
PubMed2000

Survival in patients with chronic lower extremity ischemia: a risk factor analysis.

This is a prospective cohort comparison study aiming to determine the mortality of patients with peripheral arterial occlusive disease (PAOD) and identify the risk factors affecting their survival. Data regarding demographic and biochemical risk factors, and lower limb disease severity classified by vascular laboratory criteria were collected prospectively from 665 consecutive patients presenting with symptoms of peripheral arterial occlusive disease. The effect of patient and disease risk factors on survival was analyzed by the life-table method and independent significant variables examined by a multivariate Cox regression model. The cumulative survival for all patients at 1, 3, and 5 years were 86.1, 71.2, and 55.8%, respectively, with a median survival of 72.2 months. Female sex, age, smoking, heart disease, renal disease, respiratory disease, stroke, critical ischemia, lowest anklebrachial index, no vascular reconstruction, and major amputation were associated with higher mortality. Lipid and biochemical variables were not significant determinants. Using multivariate Cox regression, age (>70), disease severity, anklebrachial index (<0.5), no vascular reconstruction, diabetes mellitus, and renal and cardiorespiratory diseases were identified as independent risk factors affecting patient survival. The survival of patients with PAOD is poor compared with the general population. Significant patient-related variables were largely coexisting diseases and advanced age, whereas the other risk factors for atherosclerosis are less influential. Disease severity may bear a direct relationship to mortality, and patients with critical ischemia have the worst prognosis. Early disease detection and timely vascular reconstruction may lead to an improvement in overall survival.

Adult↗
PubMed2000

Cumulative experience with pediatric living related liver transplantation.

PURPOSE: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. METHODS: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. RESULTS: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), alpha-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. CONCLUSION: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease.

Child↗
PubMed2000

Duration of effect of botulinum toxin type A in adult patients with cervical dystonia: a retrospective chart review.

BACKGROUND: Clinical trials have established the efficacy and safety of botulinum toxin type A (BTX-A) in patients with cervical dystonia. To maintain the clinical benefits of BTX-A, injections need to be repeated whenever patients' symptoms begin to recur. OBJECTIVE: The purpose of this study was to determine, in clinical practice settings, the mean duration of effect of BTX-A in the treatment of adult patients with cervical dystonia. METHODS: A retrospective chart review was undertaken at an academic center and a private neurology practice. At each site, > or =50 patients being treated for cervical dystonia were identified and randomized for chart review. Patients had to have received the first assessable injection of BTX-A between January 1, 1998, and March 31, 1998, to coincide with the clinical availability of the most current formulation of the neurotoxin. A chart was eligible for review if the patient was aged > or =18 years, had a documented diagnosis of idiopathic cervical dystonia, was being treated with BTX-A, and had been under the continuous care of investigators from January 1, 1998, to August 31, 1999. Of the 102 patients initially identified, the first 30 from each site who met the study inclusion criteria were assessed for (1) age and sex; (2) severity of dystonia; (3) years of BTX-A use; (4) dates of first, second, third, and fourth BTX-A injections; (5) drug dose; (6) use of electromyography; (7) use of other prescribed therapies; (8) laboratory tests; and (9) adverse events. The mean interval between each visit and mean per-patient duration of effect were calculated and stratified by patient characteristics. RESULTS: The mean age of the patients was 56.4 years. Two thirds of the patients were women. Forty-one of the 60 patients (68.3%) had either moderate or severe disease, and 48 (80.0%) had experienced cervical dystonia for >5 years. The mean per-patient duration of effect across the 4 visits was 15.5 weeks (range, 12.2-24.3 weeks). The duration of effect did not differ significantly between study sites despite the differences in disease severity, drug dose, and use of adjunctive therapy. CONCLUSION: BTX-A the controls symptoms of cervical dystonia for 12 to 24 weeks, with a mean duration of effect per patient of 15.5 weeks.

Botulinum Toxins, Type A↗
PubMed2000

Population PK and PK/PD modelling of microencapsulated octreotide acetate in healthy subjects.

AIMS: To develop a population model that can describe the pharmacokinetic profile of microencapsulated octreotide acetate in healthy cholecystectomized subjects. To investigate the correlation between serum IGF-1 and octreotide concentration. METHODS: A population pharmacokinetic analysis was performed on octreotide data obtained following a single dose of 30 mg microencapsulated octreotide acetate intramuscularly. The relationship between serum IGF-1 concentration and octreotide concentration was effectively described by a population pharmacokinetic/pharmacodynamic model. RESULTS: The pharmacokinetic profile of octreotide was characterized by an initial peak of octreotide followed by a sustained-release of drug. Plateau concentration were sustained up to day 70, and gradually declined to below the detection limit by day 112. A one-compartment linear model was constructed which consisted of two absorption processes, characterized by KIR and KSR, rate constants for immediate-release and sustained-release, respectively, with first-order elimination (Ke; 1.05 h-1). The surface, unencapsulated drug was immediately absorbed into the central compartment with first-order absorption (KIR; 0.0312 h-1), while the microencapsulated drug was first released in a zero-order fashion into a depot before being absorbed into the central compartment with first-order absorption (KSR; 0.00469 h-1) during a period of tau (1680 h). Body weight and gender were important covariates for the apparent volume of distribution. The type of formulation was an important covariate for KIR but had no effect on KSR. An inhibitory Emax population pharmacokinetic/pharmacodynamic model could adequately describe the relationship between IGF-1 (expressed as percent baseline) and octreotide concentration. Baseline IGF-1 concentration was found to be a significant covariate for the baseline effect (E0). A relationship between GH concentration and octreotide concentration was not established. CONCLUSIONS: The pharmacokinetic profile of microencapsulated octreotide acetate was effectively described by the derived population model. The relationship between IGF-1 and drug concentration could be used to guide optimization of therapeutic octreotide dosage regimens.

Adult↗
PubMed2000

Eighteen-year experience with femoro-femoral bypass.

BACKGROUND: The role of femoro-femoral bypass in the management of aorto-iliac occlusive disease has evolved during the past two decades. The aim of the present study was to evaluate the early and long-term outcomes of femoro-femoral bypass grafts performed at the University of Hong Kong Medical Centre during an 18-year period. METHODS: From 1981 to 1998, a retrospective analysis of 61 patients who underwent femoro-femoral bypass at the University of Hong Kong Medical Centre was undertaken. Data on demographic features and results of surgical intervention were reviewed. Early outcomes (morbidity, mortality and improvement of clinical category) and long-term outcomes (graft patency, patient survival and limb salvage rates) were analysed. RESULTS: The postoperative morbidity and mortality rates were 16% and 7%, respectively. Clinical success was achieved in 48 patients (79%) after operation. The primary patency of femoro-femoral bypass was 86%, 79% and 71% at 1, 3 and 5 years, respectively. The limb salvage rate was 85% at 3 years. The cumulative survival rate of the study population was 89%, 82% and 73% at 1, 3 and 5 years, respectively. CONCLUSIONS: Femoro-femoral bypass was successful in relieving ischaemic pain and limb salvage in approximately 80% of patients. A 5-year patency rate of 71% was achieved. Femoro-femoral bypass remains a valuable surgical procedure for limb salvage in poor-risk patients with unilateral iliac artery occlusion.

Aged↗
PubMed2000

Pharmacokinetics of diclofenac sodium in chronic active hepatitis and alcoholic cirrhosis.

The objective of this study was to assess the pharmacokinetics of diclofenac sodium and its five metabolites following administration of a 150 mg oral dose to healthy subjects and patients with either chronic active hepatitis of varying morphology or alcoholic cirrhosis. Six healthy subjects, 6 chronic active hepatitis patients, and 6 alcoholic cirrhosis patients were enrolled in this prospective, open-label, parallel study. Blood samples were drawn at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 312, and 480 hours, and urine samples were collected for 144 hours after administration of a single oral dose of diclofenac sodium. The mean area under the serum concentration-time curve extrapolated to infinity, oral clearance, half-life, maximal concentration, and time to peak concentration for diclofenac and its metabolites were determined and compared using analysis of variance. Cirrhotics had a mean +/- SD diclofenac AUC value (19,114 +/- 6806 ng.h/ml) significantly different (p < 0.02) from hepatitis patients (6071 +/- 1867 ng.h/ml) and healthy subjects (7008 +/- 2006 ng.h/ml), whereas healthy subjects and hepatitis patients had similar values. Comparable results were found for 4'-hydroxydiclofenac. The AUC values for 3'-hydroxydiclofenac and 3'-hydroxy-4'methoxydiclofeanc were significantly different when healthy subjects were compared to cirrhotics. However, hepatitis subjects were not significantly different from either group. The results indicate that hepatitis does not alter the pharmacokinetics of diclofenac. Alcoholic cirrhosis increased the mean diclofenac AUC approximately three times compared to normal subjects, indicating that one-third of the usual dose in cirrhotics would produce equivalent AUC values in normal subjects and subjects with alcoholic cirrhosis. However, since pharmacodynamic measurements were not made and no increase in untoward or side effects was noted in the alcoholic cirrhosis patients after a single dose, maintenance doses should be titrated to patients response.

Adult↗
PubMed2000

Population pharmacokinetics/toxicodynamics (PK/TD) relationship of SAM486A in phase I studies in patients with advanced cancers.

SAM486A (previously termed CGP 48664), a potent inhibitor of S-adenosylmethionine decarboxylase, is under clinical development for the treatment of advanced refractory malignancies. Hematological toxicity manifested by dose-dependent neutropenia has been observed in phase I studies. Population methods were used to investigate pharmacokinetics (PK) as a prognostic factor for safety end point (hematological toxicity) in patients with advanced cancers. SAM486A plasma concentrations and neutrophil counts were collected from three ascending-dose tolerability and PK studies (study 1: single 5-day continuous intravenous (IV) infusion with doses ranging from 24-700 mg/m2/cycle; study 2: 10-minute to 3-hour IV infusion once weekly with doses ranging from 16-325 mg/m2/week; study 3: 1-hour IV infusion once daily for 5 days with doses ranging from 3.6-202.8 mg/m2/day). The PK of SAM486A were best estimated by a population linear three-compartment model with NONMEM (version 5) using data from 9 patients in studies 1 through 3. The population pharmacokinetic parameters (SD) were CL = 6.2 (0.4) l/h/m2, Q2 = 15.4 (1.5) l/h/m2, Q3 = 33.6 (5.3) l/h/m2, V1 = 9.5 (1.6) l/m2, V2 = 672 (52) l/m2, and V3 = 39.9 (8.3) l/m2, and the corresponding intersubject variability was 45.4%, 74.0%, 85.3%, 80.1%, 37.0%, and 103%, respectively, where CL is total body clearance, Q2 and Q3 are intercompartmental clearances, and V1, V2, and V3 are the volumes of distribution in central and peripheral compartments, respectively. The intrasubject variability was 24.0%. The cumulative AUC before the onset of neutrophil nadir count (AUC) and the duration of exposure over threshold SAM486A concentrations in the range of 0.05 to 0.1 microM based on Bayesian PK parameter estimates significantly correlated with absolute neutrophil count nadir (< 5 x 10(9)/l). AUC showed the best correlation (R2 = 0.72) with absolute neutrophil count nadir by an inhibitory sigmoid Emax model and also correlated with percent decrease in neutrophil count from baseline to nadir by a simple Emax model (R2 = 0.53). Logistic regression analysis indicated that AUC and the duration of exposure over 0.05 to 0.1 microM, but not Cmax, were strong predictors of grade 4 neutropenia (< 0.5 x 10(9)/l). Drug exposure parameters such as AUC derived from population analysis may be used clinically as a useful predictor of drug-induced neutropenia.

Adult↗
PubMed2000

Combined long-segment angioplasty and stenting of the superficial femoral artery and popliteal-distal bypass for limb salvage.

The treatment of multisegment superficial femoral artery and tibial vessels atherosclerotic disease is traditionally a femoro-distal bypass using in situ or reversed autogenous vein. The improved result of balloon angioplasty and stenting of the superficial femoral artery (SFA) has extended its application to treat long segment SFA stenosis. A combined endovascular-open surgery approach of SFA endovascular stenting with a popliteal-distal bypass is an alternative less invasive procedure to achieve optimum distal revascularization for limb salvage.

Aged↗
PubMed2000

An audit of the early outcomes of ambulatory inguinal hernia repair at a surgical day-care centre.

Ambulatory surgery has been recently gaining popularity owing to the increasing constraints on public-sector health care resources. Inguinal hernia repair is one of the most common day-case operations. This study was conducted to audit the early outcomes of 271 consecutive day-case inguinal hernia repairs performed at the Day Surgery Centre of the Tung Wah Hospital from 1 December 1995 through 31 December 1998. No patients died on the day of their surgery; in 265 (97.8%) cases, patients were discharged home on the day of their operation. Two patients required readmission because of fever and urinary retention, and the postoperative morbidity rate was approximately 5% (14/271 cases). Wound complication was the most common morbidity encountered and pain was the most common discomfort experienced by patients at home. These results suggest that ambulatory hernia repair can be performed safely in a day centre and yields excellent early outcomes.

Adolescent↗
PubMed2000

Long-term outcome of aortofemoral bypass for aortoiliac occlusive disease.

INTRODUCTION: Revascularisation of aortoiliac occlusive disease has been evolving in the past 2 decades. The present study was undertaken to evaluate the long-term outcomes of aortofemoral bypass for aortoiliac occlusive disease at a tertiary vascular disease centre in Hong Kong. MATERIALS AND METHODS: A retrospective analysis of 94 patients (176 limbs) who survived aortofemoral bypass was performed to evaluate the graft patency, long-term complications, limb loss and patient survival rates. Thirty-six patients were operated for incapacitating claudication (Group I) and 58 for limb salvage (Group II). RESULTS: The overall primary patency rates of aortofemoral bypass were 97%, 90%, 89% and 84% at 1, 3, 5 and 10 years, respectively. Poor distal run-off and neointimal hyperplasia were the leading causes of late graft failure. Other late complications included femoral pseudoaneurysm (n = 1), infection (n = 1) and femoral graft aneurysms (n = 2). The limb loss rate was 5.1% at 4 years. The overall survival rates were 95%, 86%, 81% and 75% at 1, 3, 5 and 10 years, respectively. Ischaemic heart disease and malignancy were the 2 major causes of late death. The 5-year survival rate of group I patients (96%) was significantly superior to that of group II patients (70%). CONCLUSIONS: Aortofemoral bypass achieved a primary patency rate of 89% at 5 years and a satisfactory limb salvage rate. It remains the preferred treatment option for good risk patients with complete occlusion or extensive stenosis of the aortoiliac arteries.

Aortic Diseases↗
PubMed2000

Laparoscopic totally extraperitoneal inguinal hernioplasty: an audit of the early postoperative results of 100 consecutive repairs.

INTRODUCTION: With the establishment of a hernia specialist service at our medical centre in 1999, laparoscopic inguinal hernia repair was offered to all patients who presented with inguinal hernias. This is a report of our early experience of 100 consecutive laparoscopic totally extraperitoneal inguinal hernioplasties. MATERIALS AND METHODS: Between June 1999 and January 2000, a total of 82 patients with 100 inguinal hernias underwent laparoscopic totally extraperitoneal hernioplasties. The mean age of the study population was 64 +/- 16 (SD) years with a male to female ratio of 79:3. A prospective evaluation and analysis of perioperative outcomes were performed. RESULTS: A total of 97 laparoscopic extraperitoneal inguinal hernioplasties were successfully performed. Three patients required conversion to transabdominal preperitoneal repair because of adhesion (n = 1), large peritoneal defect (n = 1) and the presence of bowel within hernial sac (n = 1). There were no other intraoperative complications. Postoperative morbidity included retention of urine (n = 4), asymptomatic groin collection (n = 4) and wound bruising (n = 2). All complications resolved uneventfully. The visual analogue pain score at rest was 2, 1 and 1 on postoperative days 0, 1 and 2, respectively. The mean length of hospital stay was 2 +/- 1 (SD) days. Forty-seven patients (57%) returned to normal activities within one week. CONCLUSIONS: The early outcomes of laparoscopic extraperitoneal inguinal hernioplasties were encouraging. It confirmed the early success of laparoscopic repairs of inguinal hernias at our centre. Laparoscopic approach is a safe technique for repair of inguinal hernia in specialised centres.

Adult↗
PubMed1999

Long-term complete remission and immune tolerance after intensive chemotherapy for lymphoproliferative disorders complicating liver transplant.

BACKGROUND: B cell lymphoproliferative disorders (LPD) and liver rejection are major lethal complications after hepatic transplantation. Reduction in immunosuppression is the treatment for the former, but is a risk factor for the latter. METHODS: Here, we report three consecutive children with monoclonal LPD complicating orthotopic liver transplantation. All of them were treated with brief (<4 months) but intensive chemotherapy. RESULTS: These three patients have remained in complete remission for LPD for 18 months to more than 3 years. Aggressive antimicrobial prophylaxis was successful in preventing life-threatening infections. The patient who received the highest cumulative doses of chemotherapy may have also developed relative immune tolerance to the allograft. CONCLUSIONS: High-dose-intensity chemotherapy may be effective in the treatment of monoclonal LPD, as well as in the induction of immune tolerance for the prevention of allograft rejection and LPD recurrence.

Acyclovir↗