Search PubMed⌕ Search

Biomedical subjects

W K Cheung

Publications and source records attributed to W K Cheung.

At least 19 recordsLinked to original sources
PubMed2000

Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizers.

This report summarizes the results of two double-blind, single-center, randomized studies that used a two-period crossover design. The objective of these two studies was to compare the safety, tolerability, pharmacokinetics, and pain score at the subcutaneous (sc) injection site of a phosphate-buffered recombinant human erythropoietin (EPREX, epoetin alfa, r-HuEPO) formulated with a new stabilizer (glycine and Polysorbate 80) with the commercially available EPREX formulations, which uses human serum albumin (HSA) as the stabilizer. Twenty-four healthy male volunteers were enrolled in each of the two studies. In the first study, subjects received a single 150 IU/kg sc dose of r-HuEPO using the 2000 IU/mL (2K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In the second study, subjects received a single 750 IU/kg sc dose of r-HuEPO using the 40 000 IU/mL (40K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In each study, r-HuEPO was administered over two separate dosing periods, each separated with a 28-day washout period. There were no significant differences in AUC and C(max) for either strength of r-HuEPO formulated with or without the new stabilizer, indicating that the absorption and disposition characteristics of the two formulations were similar after sc administration. Both r-HuEPO strengths with and without the new stabilizer were safe and well tolerated; the safety and tolerability profiles of both formulations for each r-HuEPO concentration were comparable. There were no statistically significant differences in pain score for either strength of r-HuEPO with and without the new stabilizer. It was concluded that the two phosphate-buffered r-HuEPO concentrations formulated with and without the new stabilizer are pharmacokinetically equivalent.

Adolescent↗
PubMed2000

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

Patients with long-standing diabetes commonly suffer from gastric neuromuscular dysfunction (gastropathy) causing symptoms ranging from postprandial bloating to recurrent vomiting. Autonomic neuropathy is generally believed to be responsible for diabetic gastropathy and the underlying impairments in gastric emptying (gastroparesis) and receptive relaxation, but the specific mechanisms have not been elucidated. Recently, it has been recognized that interstitial cells of Cajal generate electrical pacemaker activity and mediate motor neurotransmission in the stomach. Loss or defects in interstitial cells could contribute to the development of diabetic gastroparesis. Gastric motility was characterized in spontaneously diabetic NOD/LtJ mice by measuring gastric emptying and by monitoring spontaneous and induced electrical activity in circular smooth muscle cells. Interstitial cells of Cajal were studied by Kit immunofluorescence and transmission electron microscopy. Diabetic mice developed delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent. Our observations suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy.

Animals↗
PubMed1998

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects.

OBJECTIVES: To understand the pharmacokinetic and pharmacodynamic properties of recombinant human erythropoietin (epoetin alfa) and to continue to optimize dosing regimens by determining whether administration of single high doses of epoetin alfa is as effective as repeated administration. METHODS: Epoetin alfa was administered as single subcutaneous doses of 300, 450, 600, 900, 1200, 1350, 1800, and 2400 IU/kg and in multiple subcutaneous dose regimens: 150 IU/kg 3 times a week for 4 weeks and 600 IU/kg once per week for 4 weeks in 2 open-label, randomized placebo-controlled studies in healthy volunteers. RESULTS: The absorption rate of epoetin alfa after subcutaneous administration was independent of dose, whereas clearance was dose-dependent in that it decreased with increasing dose. There was a linear relationship between response measured as percentage of reticulocytes area under the curve (AUC) and erythropoietin AUC for single doses up to 1800 IU/kg. Beyond the 1800 IU/kg dose, there was a saturation of response. The mean percentage of reticulocytes after single-dose regimens began to increase by days 3 to 4, reached their maximum at days 8 to 11, and returned to baseline values by day 22. In contrast, the mean percentage of reticulocytes after both multiple-dose regimens were maintained above baseline values through day 22 as both regimens stimulated modest but sustained increases in percentage of reticulocytes (1% to 2%). The mean percentage of reticulocytes AUC for 600 IU/kg epoetin alfa given once a week for 4 weeks was apparently greater than the mean percentage of reticulocytes AUC for 150 IU/kg 3 times a week for 4 weeks. Although daily oral iron supplementation was given, mean serum ferritin levels declined by approximately 75% through day 22 in subjects treated with multiple doses of epoetin alfa. CONCLUSIONS: These findings show that the pharmacologic response to epoetin alfa is a function of dose and dosing regimen. Repeated administration of epoetin alfa was more effective in stimulating a reticulocyte response than single-dose administration of the same total amount of epoetin alfa.

Adult↗
PubMed1998

Conjunctivitis caused by Thelazia callipaeda infestation in a woman.

Thelazia is a nematode (Spirurida) that can parasitize the mammalian conjunctival sac. This is the first reported case of ocular. Thelazia callipaeda infestation in Taiwan. A 41-year-old woman experienced swelling, itching sensation and occasional blurred vision of the right eye 2 weeks after a small group of flies swarmed her eye while she was hiking. Her symptoms were first misdiagnosed as allergic conjunctivitis at a local medical clinic. During her first visit to our outpatient department, five white thread-like living worms were discovered on the superior and inferior fornices. The worms were cream-colored, slender and approximately 1 cm in length. Follicular and papillary conjunctivitis was noted in her right eye. After removing the worms, the symptoms resolved and no other worms were found in the following 2 months. This case is a remainder to physicians that parasitic infestation should be included in the differential diagnoses of ocular itching, conjunctivities, and blurred vision after insect contact.

Adult↗
PubMed1997

Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses.

The pharmacokinetics of once-daily oral levofloxacin (study A) or intravenous levofloxacin (study B) in 40 healthy male volunteers were investigated in two separate randomized, double-blind, parallel-design, placebo-controlled studies. Levofloxacin at 500 mg or placebo was administered orally or intravenously as a single dose on day 1; daily oral or intravenous dosing resumed on days 4 to 10. In a third study (study C), the comparability of the bioavailabilities of two oral and one intravenous levofloxacin formulations were investigated with 24 healthy male subjects in an open-label, randomized, three-way crossover study. Levofloxacin at 500 mg as a single tablet or an intravenous infusion was administered on day 1; following a 1-week washout period, subjects received the second regimen (i.e., the other oral formulation or the intravenous infusion); the third and final regimen was administered following a 1-week washout period. The concentrations of drug in plasma and urine were measured by validated high-pressure liquid chromatography methods. Pharmacokinetic parameters were estimated by noncompartmental methods. In both study A (oral levofloxacin) and study B (intravenous levofloxacin), steady state was attained within 48 h after the start of the multiple dosing on day 4. Levofloxacin pharmacokinetics were linear and predictable for the single and multiple 500-mg, once-daily oral and intravenous dosing regimens, and the values of the pharmacokinetic parameters for the oral and intravenous administrations were similar. Study C indicated that levofloxacin was rapidly and completely absorbed from the oral tablets, with mean times to the maximum concentration of drug in serum of approximately 1.5 h and mean absolute bioavailability of > or =99%. These results support the interchangeability of the oral and intravenous routes of levofloxacin administration.

Administration, Oral↗
PubMed1996

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy.

PURPOSE: This study was designed to evaluate the absolute bioavailability (F value) of 2-chlorodeoxyadenosine (cladribine; 2-CdA) after multiple oral administrations, and the intersubject variability after oral and 2-hour intravenous (IV) administration schedules in patients with malignancy. PATIENTS AND METHODS: Patients with advanced malignancies were eligible. There were two treatment cycles; during cycle 1, patients received 2-CdA solution at 0.28 mg/kg/d orally under fasting conditions for 5 consecutive days concomitantly with omeprazole, and 4 weeks later during cycle 2 patients received 2-CdA as a 2-hour IV infusion of 0.14 mg/kg/d for 5 consecutive days. Serial blood samples for 2-CdA plasma levels were obtained after drug administrations on days 1 and 5 during each treatment cycle. RESULTS: Ten patients completed cycles 1 and 2. The F value of oral 2-CdA measured on days 1 and 5 was 37.2% and 36.7%, respectively. For both oral and IV multiple administrations, there was no significant accumulation in maximum concentration (Cmax), and the intersubject variabilities (coefficient of variation [CV], approximately 40%) in Cmax and area under the concentration-time curve from 0 to 24 hours [AUC(0-24)] values were comparable for both routes on days 1 and 5. A three-compartment open model was applied to the plasma concentration data after oral and IV administrations and resulted in good agreement between observed and simulated concentration-time profiles. Neutropenia was the principal adverse event observed when 2-CdA was administered orally and IV. CONCLUSION: The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

Administration, Oral↗
PubMed1995

Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.

PURPOSE: The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. METHODS: Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. RESULTS AND CONCLUSIONS: The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (approximately 20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).

Administration, Oral↗
PubMed1995

Acute intracranial subdural haematoma resulting from lumbar myelography.

We report a case of acute intracranial subdural haematoma after lumbar myelography with Iopamidol. The haematoma was successfully treated by emergency craniotomy. The bleeding came from cortical bridging veins as confirmed by surgery. This rare complication should be suspected in patients who complain of prolonged headache or develop a neurological deficit after myelography.

Acute Disease↗
PubMed1994

Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'-monophosphate increases hypothalamic levels of neuropeptide Y.

This investigation examined in vivo the relationship between the nucleotide cAMP and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL), which are known to potentiate feeding behavior. In brain-cannulated rats, third ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the paraventricular nucleus (mPVN), while having no impact in other hypothalamic areas. These site-specific changes in NPY occurred in the absence of any alteration in circulating levels of insulin, corticosterone, aldosterone or glucose, or of changes in hypothalamic levels of GAL. These findings implicate cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing neurons, projecting from the ARC to the mPVN, that are believed to be involved in energy homeostasis.

Aldosterone↗
PubMed1994

Biochemical identification of citrobacteria in the clinical laboratory.

We biochemically identified 235 Citrobacter strains to the species level on the basis of the recently proposed taxonomic changes of Brenner et al. (D. J. Brenner, P. A. D. Grimont, A. G. Steigerwalt, G. R. Fanning, E. Ageron, and C. F. Riddle, Int. J. Syst. Bacteriol. 43:645-658, 1993). Citrobacter isolates were initially identified as C. koseri or as members of the C. freundii complex or C. amalonaticus group on the basis of indole production, formation of H2S, malonate utilization, and acid production from D-arabitol and adonitol. On the basis of the results of these tests, 68% of the Citrobacter strains were identified as members of the C. freundii complex, 25% were C. koseri, and 8% were members of the C. amalonaticus group. By using a 15-test system recently proposed by Brenner et al. (D. J. Brenner, P. A. D. Grimont, A. G. Steigerwalt, G. R. Fanning, E. Ageron, and C. F. Riddle, Int. J. Syst. Bacteriol. 43:645-658, 1993) to help identify new species in the C. freundii complex and C. amalonaticus group, 81% of the C. freundii complex strains and 100% of the C. amalonaticus strains could be definitively assigned to one of the previously established or recently designated species or hybridization groups of the genus Citrobacter. Within the C. freundii complex, C. freundii predominated overall (37%), followed by C. youngae (24%), C. braakii (13%), and C. werkmanii (6%). Only one strain each of C. sedlakii and Citrobacter DNA group 11 was identified in this study. Among C. amalonaticus complex members, all were identified as C. amalonaticus with the singular exception of one fecal isolate of C. farmeri. C. freundii and C. koseri were the two Citrobacter species most commonly (80 of 93 [86%]) isolated from extraintestinal sources (genitourinary tract, wounds, blood).

Bacterial Typing Techniques↗
PubMed1994

Incomplete forms of Beckwith-Wiedemann syndrome: report of a case.

Beckwith-Wiedemann syndrome is a rare disease characterized by a constellation of congenital and time-dependent abnormalities such as defects of the abdominal wall, gigantism, craniofacial dysmorphism, visceromegaly and hemihypertrophy. The syndrome is divided into complete and incomplete forms and, as it may only have subtle phenotypic features, it is easily neglected by clinicians. Patients with this syndrome, particularly those associated with hemihypertrophy, have a high risk of growing malignant tumors. This is a case report of a patient with an incomplete form of this syndrome with left hemihypertrophy, hepatosplenomegaly and a small right adrenal cystic lesion.

Adult↗
PubMed1993

Meal patterns and macronutrient intake after peripheral and PVN injections of the alpha 2-receptor antagonist idazoxan.

Studies with idazoxan (IDA), a specific alpha 2-noradrenergic receptor antagonist, demonstrate effects on feeding behavior opposite to those observed with norepinephrine in the paraventricular nucleus (PVN) and peripheral injection of the alpha 2 agonist clonidine. Administration of IDA, both intraperitoneally (IP) and into the PVN at the onset of the nocturnal feeding cycle, caused a dose-related, selective suppression of carbohydrate intake 90 min after injection. To characterize further the impact of this antagonist on macronutrient intake, we examined in IDA-injected animals the macrostructure of feeding using computer-assisted analyses of meal patterns. Both IP and PVN administration of IDA produced a selective suppression of carbohydrate intake, primarily during the first meal of the feeding cycle. This effect occurred through significant reductions in meal size, diet composition, feeding time, and feeding rate for this nutrient. Idazoxan administration into the PVN continued to decrease carbohydrate intake in the next two meals and reduced the satiating impact of this nutrient. In contrast to this immediate change in carbohydrate intake, PVN IDA reduced protein intake after a latency of 4 h. although fat intake was suppressed only after a latency of 7 h. An increase in total meal number and a decrease in the average meal size across the 12-h dark cycle were seen after PVN IDA administration. These results, showing effects of peripheral and PVN-injected IDA on carbohydrate intake, suggest a possible physiological role of endogenous PVN alpha 2-noradrenergic receptors in modulating natural patterns of carbohydrate feeding at the onset of the dark period.

Adrenergic alpha-Antagonists↗
PubMed1993

Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection.

Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle.

Animals↗
PubMed1992

Identification of Aeromonas strains to the genospecies level in the clinical laboratory.

One hundred thirty-three strains of Aeromonas (human, n = 102; animal, n = 16; environmental, n = 15) previously identified to the DNA group level by molecular methods were biochemically analyzed for 58 properties. On the basis of the use of between 9 and 16 selected tests, 132 of the 133 strains (99%) could be assigned to their correct hybridization group using this biochemical scheme. The results suggest a feasible approach for identifying aeromonads to genospecies level under appropriate conditions.

Aeromonas↗
PubMed1992

Radiological manifestations of cardiovocal syndrome.

Cardiovocal syndrome is a rare clinical diagnosis that signifies vocal cord palsy associated with various cardiovascular diseases. The radiological manifestations of six cases of clinically diagnosed cardiovocal syndrome are reviewed retrospectively. The common clinical presentation of these six cases was hoarseness that was due to left vocal cord palsy. By means of chest X-rays (CXR) and cardioangiography, four cases were respectively diagnosed to have atrial septal defect (n = 1), ventricular septal defect (n = 1) and mitral stenosis (n = 2), all of which were associated with a common radiological finding of dilatation of pulmonary trunk. The other two cases were separately diagnosed to have proximal descending aortic saccular aneurysm (n = 1) by means of CXR and angiography, and fusiform ascending aortic aneurysm (n = 1) by computed tomography and magnetic resonance image. All these radiological presentations of either aortic aneurysm or dilated pulmonary trunk were associated with encroachment of aorticopulmonary window for which the left recurrent laryngeal nerve was presumably compressed with the result of left vocal cord palsy. Hoarseness that is caused by these underlying cardiovascular diseases is correctable after treatment of the underlying diseases. Hence, clinicians and radiologists should pay attention to the radiological manifestations of patients whose chief complaints are hoarseness and cardiovocal syndrome.

Adult↗
PubMed1991

Pharmacokinetic principles in the design of immediate-release components in sustained-release formulations with zero-order release characteristics.

The potential advantages and disadvantages of incorporating an immediate-release (IR) component in sustained-release formulations with zero-order release characteristics (SR) are discussed. The dose of the IR component for SR doses other than the first one (DIS) should be less than that for the first SR dose (DI). Multiple dosing of an SR formulation with an IR component of dose DI may lead to unnecessary accumulation and fluctuation of plasma drug concentrations. An innovative and practical method for estimating the DI and DIS doses of this IR component is also presented.

Chemistry, Pharmaceutical↗