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Biomedical subjects

B Cheung

Publications and source records attributed to B Cheung.

At least 19 recordsLinked to original sources
PubMed1997

Intravenous and oral pharmacokinetic evaluation of a 2-hydroxypropyl-beta-cyclodextrin-based formulation of carbamazepine in the dog: comparison with commercially available tablets and suspensions.

Complexation of carbamazepine with 2-hydroxypropyl-beta-cyclodextrin was performed to provide improved formulations of this widely used antiepileptic drug. Based on this approach, liquid dosage forms were configured for both parenteral and oral use. Intravenous administration of an aqueous carbamazepine x 2-hydroxypropyl-beta-cyclodextrin (CBZ x HPbetaCD) complex at a CBZ dose of 20 mg/kg was well tolerated and generated high initial drug levels that fell monoexponentially as a function of time, yielding a plasma elimination half-life of 38 min. Oral studies were completed with three preparations: a commercially available tablet and suspension, as well as a CBZ x HPbetaCD oral solution. Oral administration of tablets gave erratic and slow absorption, leading to maximum CBZ concentrations (C(max)) of <2 microg/mL, which were manifested only at 2.5 h after drug dosing. The absolute bioavailability of CBZ from the tablets was approximately 25%. Both the suspension and CBZ x HPbetaCD solution gave a significantly improved profile. Thus, the liquid oral dosage forms approximately doubled the oral bioavailability of CBZ compared with the tablets.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1997

Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal disorders.

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide. 2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l), congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5 pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P < 0.05), confirming previous reports. 4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.

Adrenomedullin↗
PubMed1996

Retinoic acid receptors beta and gamma distinguish retinoid signals for growth inhibition and neuritogenesis in human neuroblastoma cells.

Retinoids induce marked growth inhibition and neuritic differentiation in human neuroblastoma cells. Expression patterns of nuclear retinoic acid receptors (RAR) in embryonic and adult tissues suggests that RAR subtypes alpha, beta and gamma have tissue-specific functions. We have transfected a human neuroblastoma tumor cell line with a vector expressing either human RAR alpha, beta or gamma cDNAs. In the absence of exogenous retinoid, RAR beta transfectants demonstrated marked growth inhibition without morphologic evidence of differentiation, whereas transfectant clones overexpressing RARs alpha and gamma had no significant reduction in cell growth rates. Although RAR gamma transfectants were sensitive to the growth inhibitory effects of exogenous retinoids, these cells demonstrated resistance to the neuritogenic retinoid effects. Only RAR beta transfectants exhibited increased sensitivity to retinoids added in vitro. These results suggest that distinct neuritogenic and growth inhibitory signalling pathways exist in neuroblastoma cells and that RAR beta expression may be necessary for the retinoid growth inhibitory pathway.

Cell Differentiation↗
PubMed1996

A case of unrelenting pursuit of castration.

OBJECTIVE: Explore the limitations of the classification of body dysmorphic disorder. CLINICAL PICTURE: A chinese male relentlessly pursued castration to relieve painful erections which were never substantiated. The testes and corporaspongiosum had been removed. No psychotic symptom was prominent. TREATMENT: Cognitive therapy and psychotropics were tried. OUTCOME: The remaining corpora cavernosa was removed subsequently. CONCLUSION: The distorted somatic perception and secondary cognitive amplification (painful erections) could represent a variant of body dysmorphic disorder involving internal body image; diagnostic classifications should accommodate such a category.

Adult↗
PubMed1996

Evaluation of an intravenous heparin nomogram in a coronary care unit.

OBJECTIVE: To develop, implement and evaluate an effective and efficient heparin nomogram. DESIGN: Retrospective and prospective data collection. SETTING: Coronary care unit (CCU) of a university-affiliated hospital. PATIENTS: Patients with acute coronary ischemic syndromes requiring intravenous (i.v.) heparin who were not receiving thrombolytic and/or warfarin therapy. INTERVENTIONS: A retrospective chart review of 52 CCU patients receiving iv heparin provided the historical control group. The effectiveness of a heparin nomogram (5000 U bolus followed by an initial weight-based infusion of 15 U/kg/h with subsequent rate adjustments according to activated partial thromboplastin time [aPTT] results) was then prospectively assessed in a further 56 consecutive patients. MAIN RESULTS: The historical control and nomogram groups did not significantly differ with respect to age, weight, duration of therapy or total number of aPTTs drawn. Approximately 79% and 84% of patients in the control and nomogram groups, respectively, achieved an aPTT within the therapeutic range (60 to 90 s, P > 0.05), whereas 89% and 100% of control and nomogram patients, respectively, surpassed the therapeutic threshold (longer than 60 s) at some point during treatment (P = 0.009). Compared with empiric dose adjustment, the nomogram more effectively avoided periods of inadequate anticoagulation. Similarly, the time to achieve the therapeutic threshold was significantly longer in the control than in the nomogram group (8.2 +/- 5.9 versus 6.7 +/- 3.7 h, P = 0.026). No adverse bleeding events were noted in either group. CONCLUSIONS: Compared with conventional approaches, the heparin nomogram successfully achieved and maintained adequate anticoagulation in a greater proportion of patients with acute cardiovascular diseases without the need for additional aPTT measurements.

Acute Disease↗
PubMed1995

Increased retinoic acid receptor gamma expression suppresses the malignant phenotype and alters the differentiation potential of human neuroblastoma cells.

Human neuroblastoma (NB) tumor cell lines treated in vitro with the retinoid, all-trans-retinoic acid (aRA), form neurites and undergo growth arrest. Retinoids exert their diverse morphologic effects through a signalling pathway which involves the nuclear retinoid receptors. Defective retinoic acid receptor (RAR) function contributes to the malignant phenotype of several human and experimental tumors. Considerable evidence from gene disruption studies now suggests that one of the RARs, RAR gamma, may directly mediate some retinoid effects on embryonic and malignant cells. We, firstly, examined primary NB tumor tissue for a correlation between endogenous RAR gamma expression and clinical stage of the tumor and secondly, the effects of exogenous over-expression of the RAR gamma gene on a human NB tumor cell line. RAR gamma mRNA expression in 32 primary NB tumor tissue samples were significantly higher in clinically localised tumors compared with advanced or disseminated tumors. The human NB tumor cell line, BE(2)-C, was stably transfected with a mammalian expression vector (pREP4) over-expressing the human RAR gamma cDNA. Two selected clones over-expressing RAR gamma (BE/G1 and 2) exhibited a reduced growth rate compared to control cells. Tumorigenicity was inhibited for BE/G1 cells and there was a delayed onset to tumor formation for BE/G2 cells. aRA caused growth inhibition but not neuritic differentiation of the BE/G clones, while 9-cis-retinoic acid caused both growth arrest and neuritic differentiation. Taken together these results suggest that reduced endogenous RAR gamma expression may contribute to the malignant phenotype of human NB. In NB cells the retinoid signalling pathway for neuritic differentiation may be distinct from that causing growth inhibition.

Adrenal Glands↗
PubMed1995

Human stomach class IV alcohol dehydrogenase: molecular genetic analysis.

A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high Km values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the coenzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH.

Alcohol Dehydrogenase↗
PubMed1995

Spatial disorientation-implicated accidents in Canadian forces, 1982-92.

In a recent survey of CF18 aircrew human factors, 44% of pilots reported experience with spatial disorientation (SD), of whom 10% had experienced more than 3 episodes. In order to investigate further, we have completed a retrospective study of SD-implicated category A accidents (where an aircraft is destroyed, declared missing, or damaged beyond economic repair) in the Canadian Forces (CF) during 1982-92. An overview of all SD occurrences (including accidents and incidents) across aircraft types is also presented. Information was gathered concerning the genesis and severity of disorientation so that research effort and pilot training could be appropriately implemented. Mishap investigation summaries involving category A accidents where SD was implicated were obtained from the CF Directorate of Flight Safety and reviewed. We also examined in detail the Board of Inquiry Reports of these accidents. The role of disorientation in these accidents was assessed. There were 62 category A accidents between 1982-92 and, in 14, SD had been assigned as a possible cause factor in the accident records. When divided into the categories of Recognized SD (RSD), Unrecognized SD (USD), and Incapacitating SD (ISD), all but two fell into the category of USD (the pilots were unaware of the disorientation). Of the SD accidents, 11 involved a total loss of 24 lives. The majority of the accidents happened during the day, and pilots' cumulative flying experience did not appear to be a significant factor. According to our assessment, there were two episodes of vestibular origin, involving the somatogravic illusion. Three episodes of disorientation occurred over frozen lakes, one over glassy water, and one over ocean.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Aviation↗
PubMed1994

Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma.

The MRP gene (Cole et al., Science (Washington DC), 258: 1650-1654, 1992) encodes a membrane-bound glycoprotein the expression of which correlates with non-P-glycoprotein-mediated multidrug resistance in a variety of cultured human cell lines. Using an RNA-polymerase chain reaction assay, expression of this gene was examined in the highly chemoresistant pediatric malignancy, neuroblastoma. MRP expression was observed in 5 human neuroblastoma cell lines and in all 25 primary neuroblastoma tumors of stage I through IVS. Tumors with amplification of the N-myc oncogene were found to have significantly higher MRP expression that those with no amplification (P = 0.0016). Expression of the MRP gene in the tumor specimens was highly correlated with expression of the N-myc gene (P = 0.0009), while expression of the MDR1 gene, encoding P-glycoprotein, was not related to expression of either the N-myc or MRP genes. Decreased expression of the N-myc oncogene in neuroblastoma cell lines SH-SY5Y and BE(2)-C, following treatment with retinoic acid, was paralleled by down-regulation of MRP gene expression, contrasting with increased expression of the MDR1 gene. Expression of the MRP gene is thus common in both primary neuroblastoma tumors and cultured cell lines, and correlates with amplification and overexpression of the N-myc oncogene, which is central to the malignant phenotype of this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗