Biomedical subjects

A H Lau

Publications and source records attributed to A H Lau.

At least 19 recordsLinked to original sources

PubMed2003

Dendritic cells and immune regulation in the liver.

Hepatic dendritic cells (DC) unquestionably play important roles in the induction and regulation of immune responses. Due to their paucity, functional characterisation of these important antigen presenting cells has been slow but use of DC growth factors (in particular GM-CSF and Flt3L) that markedly enhance their numbers has proved helpful in furnishing adequate study material. While there is growing evidence that DC function is affected in the pathogenesis of liver disease, most work to date has been performed on non-hepatic DC. Increasing knowledge of hepatic DC biology is likely to improve our understanding of disease pathogenesis and resistance to and therapy of liver disease.

Antigens, CD↗

PubMed2003

Liver tolerance mediated by antigen presenting cells: fact or fiction?

Possible mechanisms by which liver antigen presenting cells (APC) may facilitate tolerance induction are discussed. Tolerance may be facilitated by a distinctive combination of factors, linked to the unique anatomical and microenvironmental features of the liver.

Antigen-Presenting Cells↗

PubMed2003

Long-term therapy with paricalcitol for secondary hyperparathyroidism in hemodialysis patients.

PURPOSE: The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P). PATIENTS AND METHODS: Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values. RESULTS: Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy. CONCLUSION: During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.

Adult↗

PubMed2002

The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients.

AIMS: Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. PATIENTS AND METHODS: Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. RESULTS: Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. CONCLUSIONS: Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.

Adult↗

PubMed2001

Immunologically induced histamine release from rat peritoneal mast cells is enhanced by low levels of substance P.

Although direct activation of mast cells by high concentrations (>10(-6) M) of substance P is well established, the effect of sub-micromolar concentrations of the neuropeptide on mast cell activation has not been reported. We hence investigated if substance P would modulate immunologic activation of mast cells by studying the effect of the neuropeptide on anti-rat immunologlobulin E antibody (anti-IgE)-induced histamine release from purified rat peritoneal mast cells. We observed that substance P could dose-dependently potentiate anti-IgE-induced histamine release from rat peritoneal mast cells at concentrations (3x10(-9) M to 3x10(-7) M) which alone induced insignificant or low level of histamine release. While the potentiating effect of substance P was not suppressed by any of the non-peptide tachykinin receptor antagonists CP99994 ((2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), SR48968 ((S)-N-methyl-N-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) butyl-benzamide) and SR142801 ((S)-(N)-(1-[3-(1-benzoyl-3(3,4-dichlorophenyl)piperidine-3-yl)propyl]-4-phenylpiperidin-4-yl)-N-methyl-acetamide), it was mimicked by compound 48/80 and suppressed by benzalkonium chloride. Hence, substance P enhanced anti-IgE-induced histamine release through a similar receptor-independent mechanism as the direct mast cell activating action of polybasic compounds. Since high concentrations of substance P required for directly activating mast cells may not be achievable physiologically, the enhancing actions of the neuropeptide on the immunologic activation of mast cells may be more clinically relevant in the pathogenesis of various inflammatory conditions.

Animals↗

PubMed1999

Rapid estimation of creatinine clearances in patients with liver dysfunction.

Different methods are available for rapid assessment of renal function using the patient's serum creatinine concentration and body weight without obtaining urine collection over 24 hr. However, the reliability of these methods in patients with liver diseases has not been established. The purpose of this study was to determine the accuracy and precision of the estimated creatinine clearances obtained by the methods of Cockcroft-Gault, Jelliffe, Mawer, and Siersbaek-Nielsen in patients with liver diseases who have different degrees of renal function. Creatinine clearances obtained from 24-hr urine collection were used as the standard. The different methods for rapid renal function estimation had limited accuracy and reliability in patients with severe liver dysfunction (Child-Pugh class C) and also in those with creatinine clearances of less than 60 ml/min. Creatinine clearances were overestimated by about 40-100%. Using lean body weights, instead of total body weights, reduced the prediction errors. In patients with mild liver dysfunction (Child-Pugh class A), all four estimation methods provided reasonable estimation of the creatinine clearances.

Adult↗

PubMed1999

Apoptosis induced by cisplatin nephrotoxic injury.

An agent often used in cancer treatment, cisplatin may cause acute renal failure after even a single dose. Recent laboratory studies confirmed the induction of renal cell apoptosis by cisplatin. Reduction in cell viability as well as increase in the number of cells with fragmented nuclei correlated with cisplatin exposure in a dose-dependent manner. Gel electrophoresis revealed the presence of a characteristic laddering pattern which was preceded by an increase in caspase-3 activity. As the cisplatin concentration increased beyond 50 microM, the elevation of caspase-3 activity declined, which suggests that necrosis, instead of apoptosis, is more likely to be responsible for cell death secondary to higher cisplatin concentrations. Elucidation of the molecular mechanisms of cisplatin nephrotoxicity may lead to the development of a novel therapeutic strategy that targets cancer cell death while simultaneously minimizing renal injury.

Animals↗

PubMed1999

PROBES: a framework for probability elicitation from experts.

A decision analytic model represents uncertainties as probability distributions. These distributions are hard to assess especially for large and dynamic models. We propose an integrated framework that facilitates elicitation of the relevant probability distributions for dynamic decision models from the domain experts. The experts usually use some judgmental heuristics to aid probability assessments; the resulting distributions may be proned to cognitive biases. Our framework aims to minimize the effects of these biases and to improve the quality of decisions made. We have implemented a prototype system of the framework and evaluated its effectiveness via a case study in the follow-up management of colorectal cancer patients after curative surgery. Preliminary results demonstrate the practical promise of the framework.

Colorectal Neoplasms↗

PubMed1999

Using activity-based costing to track resource use in group practices.

Research shows that understanding how resources are consumed can help group practices control costs. An American Academy of Orthopaedic Surgeons study used an activity-based costing (ABC) system to measure how resources are consumed in providing medical services. Teams of accounting professors observed 18 diverse orthopedic surgery practices. The researchers identified 17 resource-consuming business processes performed by nonphysician office staff. They measured resource consumption by assigning costs to each process according to how much time is spent on related work activities. When group practices understand how their resources are being consumed, they can reduce costs and optimize revenues by making adjustments in how administrative and clinical staff work.

Accounting↗

PubMed1998

Phosphate-binding capacities of calcium and aluminum formulations.

Calcium and aluminum phosphate binders are used to treat hyperphosphatemia which is responsible for the development of osteodystrophy commonly seen in patients with end-stage renal disease. The purpose of this study was to determine the phosphate binding capacities of several frequently used calcium and aluminum formulations. The effect of formulation types on phosphate binding was evaluated. Calcium and aluminum phosphate binders were administered to six healthy volunteers after phosphate load on separate study days. Total urine outflow was collected afterwards to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The amounts of urinary phosphate recovered were different after administration of the phosphate binders. Calcium acetate resulted in the least amount of phosphate excreted. Calcium carbonate suspension, when compared with the tablet formulation, caused a smaller amount of phosphate excreted in the urine. Different phosphate binders formulations were found to have different phosphate binding capacities. Patients should therefore be closely monitored for efficacy after switching from one phosphate binder to another.

Acetates↗

PubMed1997

Effect of obesity on pharmacokinetics and biologic effect of interferon-alpha in hepatitis C.

To examine potential adverse effects of obesity in reducing the response to interferon-alpha (IFN-alpha) in chronic hepatitis C (HCV), IFN-alpha and HCV RNA levels in serum and the 2',5'-oligoadenylate synthetase (2-5 OAS) levels in peripheral blood mononuclear cells (PBMC) were compared between six obese and five nonobese patients before and after a single, 10 mIU dose of IFN-alpha2b. There were no differences in the mean histologic activity index between the two groups. The maximal IFN concentration and the area under the serum IFN concentration-time curve were higher in nonobese patients. These two parameters were inversely correlated with body weight and body surface area. No differences were found in the mean reduction in HCV RNA levels between the two groups following IFN-alpha. The maximal 2-5 OAS level after treatment divided by the pretreatment 2-5 OAS level (2-5 OAS response ratio) was greater in the nonobese patients, suggesting stronger biologic response upon exposure to exogenous IFN-alpha in nonobese patients.

2',5'-Oligoadenylate Synthetase↗

PubMed1997

Pharmacokinetics and safety of tiagabine in subjects with various degrees of hepatic function.

PURPOSE: To evaluate the pharmacokinetics and safety of multiple oral doses of tiagabine HCl in subjects with different degrees of hepatic impairment. METHODS: Four subjects with mild hepatic impairment, three subjects with moderate hepatic impairment, and six matched normal subjects received twice daily oral tiagabine HCl for 5.5 days. Serial blood specimens were obtained for 48 h after the final dose. Total and unbound tiagabine plasma concentrations were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively. Pharmacokinetic parameters were compared between the groups by analysis of covariance. RESULTS: For total tiagabine concentrations in normal subjects and subjects with mild and moderate hepatic impairment, C(max) values (mean +/- SD) were 117 +/- 54, 172 +/- 40, and 172 +/- 28 ng/ml; C(min) values were 13 +/- 4, 27 +/- 4, and 28 +/- 6 ng/ml; areas under the plasma concentration-time curve were 396 +/- 59, 633 +/- 16, and 675 +/- 32 ng x h/ml, and elimination half-lives (harmonic means) were 7, 12, and 16 h, respectively. Unbound tiagabine concentrations, area under the unbound plasma concentration-time curve, and the free fractions were increased in the hepatically impaired subjects. Reduced serum albumin and alpha1-acid glycoprotein concentrations may have contributed to increases in the unbound fraction. Adverse events observed included dizziness, tremor, nausea, somnolence, incoordination, and unsteady gait. The frequency of these events was increased in the subjects with liver impairment. CONCLUSIONS: Because of the decreased drug elimination caused by liver function impairment, reduced doses or increased dosing interval or both may be needed to attain therapeutic plasma drug concentrations. Time to reach steady state also may be prolonged. The patients should be monitored closely for potential neurologic adverse events.

Administration, Oral↗

PubMed1996

Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin.

The effects of acute or chronic ethanol on serotonin (5-HT)-induced membrane hyperpolarization and inhibition of the slow Ca2(+)-dependent after hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 microM) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 microM buspirone, a weak 5-HT1A agonist. 5-HT (1-30 microM) also partially inhibited (approximately 40%) the sAHP following a burst of five or more action potentials. Initially ethanol (30 mM) alone did not alter the sAHP, but over a period of 38 min, a slow increase in amplitude (approximately 40%) was observed. 5-HT-mediated inhibition of the sAHP was significantly greater with ethanol present, regardless of the length of exposure. Pyramidal neurons in hippocampal slices prepared from ethanol-dependent animals showed no obvious signs of withdrawal related hyperexcitability and neither concentration-dependent membrane hyperpolarization nor sAHP inhibition caused by 5-HT were significantly changed from responses in controls. These results suggest that hyperpolarizing responses to 5-HT in hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol acutely, but does not show an adaptive change as a result of ethanol dependence.

Animals↗

PubMed1996

Gender effect on diuretic response to hydrochlorothiazide and furosemide.

Gender has been shown to elicit differences in drug disposition and response to therapeutic agents. We measured the diuretic response to oral hydrochlorothiazide, oral and intravenous furosemide in 6 male and 6 female normal volunteers. After fasting overnight, each subject received single doses of the individual diuretics or no treatment on 4 separate days. Total urine output was collected over the next 24 hours for volume measurement and determination of sodium and potassium concentrations. There was no statistically significant difference found between male and female subjects with respect to urine flow rate, sodium, and potassium excretion rates among the treatments. However, when natriuretic response was adjusted for mg/kg of the intravenous furosemide dose received, male subjects had a higher peak sodium excretion rate than the female subjects. Results of this study reveal a gender-related difference on the natriuretic response to diuretics. Further studies are necessary to identify if this gender-related difference is caused by differences in drug metabolism, disposition, or intrinsic diuretic responsiveness at the site of action.

Administration, Oral↗

PubMed1995

Estimating equilibrated Kt/V from an intradialytic sample: effects of access and cardiopulmonary recirculations.

The Smye method has been proposed to estimate the equilibrated post-dialysis BUN based on an additional intradialytic sample obtained approximately one hour into dialysis. However, the effects of access recirculation (AR) and cardiopulmonary recirculation (CPR) on the Smye computation and the corresponding details of how blood is sampled have not been studied. We examined the accuracy of two variations of the Smye technique. In one method, the intradialytic and postdialysis blood samples were obtained at full blood flow. In the other, the samples were obtained after two minutes of slow flow, to obviate the effects of both AR and CPR. Seventeen patients undergoing high efficiency dialysis and three- to four-hour treatment times were studied, in whom substantial AR was excluded based on two-minute slow flow urea rebound measurements during and just after dialysis. In this group equilibrated Kt/V (eKt/V) values computed using the Smye-derived equilibrated postBUN estimates (full flow samples, 1.22 +/- 0.058 SEM, slow flow samples, 1.23 +/- 0.064) were similar to eKt/V calculated from the 30-minute postdialysis BUN specimen (1.23 +/- 0.049, P = NS). In eight other patients with severe AR (mean 35% +/- 4.5), the accuracy of the full flow Smye estimates was poor when the degree of AR was not constant throughout the dialysis session. Accuracy of the slow flow Smye estimates of eKt/V was unaffected by the presence of severe AR. One advantage of using the full flow Smye method, however, was that a large delta Kt/V value ( < -0.40) was highly suggestive of severe AR.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

PubMed1995

Effect of diuretic drugs on creatinine clearance determination.

Diuretic drugs have been reported to alter the glomerular filtration rate and possibly the creatinine excretion by the kidneys. We evaluated the effects of single doses of diuretic drugs on creatinine clearance determination. Ten healthy volunteers were randomized to receive either oral hydrochlorothiazide, oral furosemide, intravenous furosemide, or no treatment in a cross-over fashion during four separate test days with 6-day washout periods. Urine and blood specimens were collected during 24 h after the treatments. Specimens were assayed for creatinine, and the creatinine clearance corresponding to the 4-, 6-, 12-, and 24-h urine collections were calculated. Analysis of variance did not show a statistically significant effect of the diuretic regimens on creatinine clearance over these periods. This study demonstrates that single doses of diuretic drugs do not have significant effect on creatinine clearance determination using urine collected during 4-24-h periods.

Administration, Oral↗

PubMed1995

Elimination of flucytosine by continuous hemofiltration.

Flucytosine is effective in the treatment of serious fungal infections. Some of the patients might have acute renal failure requiring continuous hemofiltration as renal replacement therapy. We evaluated the removal of flucytosine in a patient who received the drug for systemic Candida infection while undergoing continuous hemofiltration for acute renal failure. Arterial, venous, and ultrafiltrate sample pairs were collected to evaluate flucytosine removal. Ultrafiltrate/arterial drug concentration ratios and sieving coefficients obtained with the polysulfone membrane were higher than those obtained with the polyacrylonitrile membrane. Between 2.54 and 22.56 mg of flucytosine was removed from the patient per hour when the serum drug concentrations were 21.1-126.5 mg/l. The amount of hemofiltration flucytosine removal was related to ultrafiltration flow rate, serum drug concentration, and hemofilter type. The mean continuous arteriovenous hemofiltration flucytosine clearance for the polysulfone membrane was 77.0 +/- (SD) 15.6% of the ultrafiltrate flow rate, while the clearance for the polyacrylonitrile membrane was 51.0 +/- (SD) 5.7%. In patients with renal failure, continuous hemofiltration can remove an appreciable quantity of flucytosine when the ultrafiltrate flow rate is high. Serum drug concentration determination is necessary to devise an optimal dosage regimen for the patient.

Acute Kidney Injury↗

PubMed1994

Effect of continuous hemofiltration on phenytoin elimination.

Phenytoin is frequently used to treat seizure episodes in critically ill patients. Some of these patients have acute renal failure, requiring continuous hemofiltration to help maintain fluid and solute balance. We evaluated the removal of phenytoin in patients who received the drug while undergoing continuous hemofiltration treatment. Arterial and ultrafiltrate sample pairs were collected for phenytoin concentration determination. The ultrafiltrate drug concentrations were almost identical to the free serum phenytoin concentrations. Thus the ultrafiltrate/arterial drug concentration ratios resembled the percentages of serum free drug. Between 0.32 and 0.78 mg of phenytoin/h was removed by hemofiltration. The magnitude of hemofiltration phenytoin removal was related to the free drug concentration, total serum drug concentration, and ultrafiltration flow rate. When the ultrafiltration flow rate was low, the amount of phenytoin removed by hemofiltration was small relative to the usual daily dose. However, in patients with renal failure in whom serum phenytoin protein binding is substantially reduced, continuous hemofiltration at a high ultrafiltration rate may remove a clinically significant amount of the drug. Higher daily doses of phenytoin may be needed to maintain the therapeutic effect. Serum drug concentration monitoring will be necessary to determine the optimal dosage regimen.

Acute Kidney Injury↗