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Biomedical subjects

P Cheung

Publications and source records attributed to P Cheung.

At least 37 records · Page 2Linked to original sources
PubMed1999

Buprenorphine pharmacokinetics: relative bioavailability of sublingual tablet and liquid formulations.

Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM-III-R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration-time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution.

Administration, Sublingual↗
PubMed1998

Apparent thermodynamic parameters of ligand binding to the cloned rat mu-opioid receptor.

The apparent thermodynamic parameters of binding of ten ligands to the cloned rat mu-opioid receptor stably expressed in Chinese hamster ovary (CHO) cells were investigated. For every ligand, the Kd or Ki values at 0 degrees C, 12 degrees C, 25 degrees C and 37 degrees C were determined, a van't Hoff plot was generated and deltaH degrees' , deltaS degrees' and -TdeltaS degrees' and deltaG degrees' were calculated. Changes in free energy (deltaG degrees') ranged from -10.35 to -15.65 kcal/mol. The binding of sufentanil, ohmefentanyl, diprenorphine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-penicillamineThr-NH2 (CTAP) was endothermic (deltaH degrees' > 0) and driven by an increase in entropy (-TdeltaS degrees' = -13.08 to -18.57 kcal/mol). The binding of naltrexone was exothermic (deltaH degrees' = -12.56 kcal/mol) and essentially enthalpy-driven. The binding of morphine, methadone, pentazocine, [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO) and Tyr-Pro-NMePhe-D-Pro-NH2 (PL017) was exothermic (deltaH degrees' = -3.53 to -9.95 kcal/mol) and occurred with an increase in entropy (-TdeltaS degrees' = -2.48 to -7.92 kcal/mol). Plots of enthalpy versus entropy and enthalpy versus free energy were linear, although enthalpy-entropy compensation was not evident. The entropy changes were not correlated with apparent lipophilicity of the compounds. These results suggest that: (1) opioid ligands bind to the mu receptor by specific mechanisms, unrelated to lipid solubility; (2) the mechanism of binding is not universally different for peptide and non-peptide ligands; (3) the nature of binding does not a priori determine intrinsic activity. The results reveal a novel differentiation of opioid ligands into two groups (group 1: ohmefentanyl, sufentanil, diprenorphine, CTAP and PL017; group 2: naltrexone, morphine, methadone, DAMGO, pentazocine), based on two distinct relationships between enthalpy versus free energy of binding, the details of which are yet to be elucidated.

Analgesics↗
PubMed1998

Correlates of aggressive behaviour in schizophrenia: an overview.

OBJECTIVE: This review aims to critically evaluate the reported biological, psychological and social correlates of aggression in schizophrenia and to delineate those correlates which could be of use clinically and those which require further research. METHOD: The literature from 1974-1996 was searched using Psychlit and supplemented by suggestions from senior members of the authors' Department. RESULTS: Past history of aggression, psychopathology, extrapyramidal side effects of neuroleptic medications, substance abuse, reduced serotonin function, antisocial and impulsive personality traits, neurological/neuropsychological deficits, electroencephalography, neuroimaging abnormalities and environmental factors were all found to be correlated with aggressive behaviour in schizophrenia. However, there are many methodological limitations of previous studies in this field, often leading to inconsistent and inconclusive findings. CONCLUSIONS: Some tentative conclusions regarding clinically useful predictors of aggression in schizophrenia can be drawn at this stage. There is a need for methodological limitations of previous studies to be overcome before more firm conclusions can be reached.

Aggression↗
PubMed1997

Aggressive behaviour in schizophrenia: role of state versus trait factors.

The objective of this article was to elucidate the relative importance of state vs. trait factors in determining aggressive behaviour in schizophrenia. Thirty-one aggressive schizophrenia patients in rehabilitation wards were compared with 31 matched non-aggressive patients with respect to their psychopathology, phenomenologies of hallucinations and delusions, neuroleptic motor side effects, history of aggression and personality traits. Significant differences between the two groups were found in relation to psychopathology, affective responses to hallucinations/delusions, history of aggression and personality traits, but there were no significant differences regarding neuroleptic motor side effects. The effects of history of aggression as well as personality traits were independent of and similar to the total level of psychopathology, but were much smaller when compared to those of negative affective responses to hallucinations/delusions.

Adult↗
PubMed1997

Violence in schizophrenia: role of hallucinations and delusions.

The study examines the relationship between hallucinations/delusions and violent behaviour in a sample of long-stay inpatients with chronic schizophrenia. Thirty-one subjects defined as violent and meeting DSM-111-R criteria for schizophrenia were compared with 31 matched non-violent schizophrenia patients with respect to detailed phenomenologies of auditory hallucinations using the Mental Health Research Institute Unusual Perceptions Schedule (Carter and Copolov, 1993; Carter et al., 1995) and delusions using the Maudsley Assessment of Delusions Schedule (Taylor et al., 1994). Patients in the violent groups were significantly more likely to experience negative emotions, tone and content related to their voices than those in the non-violent group, whilst patients in the non-violent group were more likely to experience positive emotions, tone and content related to their voices. Patients in the non-violent group were significantly more likely to report success in coping with their voices. There was no association between command hallucinations and violent behaviour. Patients in the violent group were more likely to hold persecutory delusional beliefs than those in the non-violent group, while patients in the non-violent group were likely to hold grandiose delusions than those in the violent group. Patients in the violent group were also more likely to report that the delusion made them feel angry, while those in the non-violent group were more likely to report that the delusion made them feel elated. The results suggest specific aspects of the phenomenologies of hallucinations and delusions that should be clinically assessed to determine the likelihood of violence as a result of such psychotic symptoms.

Adult↗
PubMed1997

Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia.

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.

Adult↗
PubMed1997

Sumatriptan treatment of acute migraine attacks in a Saudi population.

Sumatriptan has been shown to be most effective in migraine attacks, but with transient, slight side effects and high rebound attack rates. We carried out a prospective study on the efficacy and safety of Sumatriptan in a Saudi population. A series of 63 consecutive out-patients with migraine histories ranging from 1/2 to 20 years were given six tablets of 100 mg Sumatriptan plus two diary cards to record the effects and side effects of the drug in two attacks per patient. Effect assessment by patients on a 4-point scale at 4 h after first medication was complemented by a 4-point scale physician's assessment. Time to resolution of attack post-medication, need for second dose (rebound attack), time lapsed to return to daily activities and side-effects were recorded. Exclusion parameters included pregnancy, lactation, hypertension, atherosclerosis, and cardiac and cerebrovascular disease. Inclusion criteria were International Headache Society (IHS)-1988 confirmed migraine characteristics and ages from 15 to 60 years. Physician assessed responses were excellent in 21 patients, good in 21, reasonable in nine and poor to nil in 12 patients. Rebound attacks necessitating second dose occurred in 25 patients. Side effects occurred in 22 (35%) patients. Sumatriptan 100 mg taken orally, is an effective and safe acute treatment mode for migraine attacks in Saudi patients.

Acute Disease↗
PubMed1997

Herpes simplex virus immediate-early proteins ICP0 and ICP4 activate the endogenous human alpha-globin gene in nonerythroid cells.

Globin genes are normally expressed only in erythroid cell lineages. However, we found that the endogenous alpha-globin gene is activated following infection of human fibroblasts and HeLa cells with herpes simplex virus (HSV), leading to accumulation of correctly initiated transcripts driven by the alpha-globin promoter. The alpha1- and alpha2-globin genes were both induced, but expression of beta- or zeta-globin genes could not be detected. Experiments using HSV mutants showed that null mutations in the genes encoding the viral immediate-early proteins ICP4 and ICP22 reduced induction approximately 10-fold, while loss of ICP0 function had a smaller inhibitory effect. Transient transfection experiments showed that ICP0 and ICP4 are each sufficient to trigger detectable expression of the endogenous gene, while ICP22 had no detectable effect in this assay. ICP4 also strongly enhanced expression of transfected copies of the alpha2-globin gene. In contrast, the adenovirus E1a protein did not activate the endogenous gene and inhibited expression of the plasmid-borne alpha2-globin gene. Previous studies have led to the hypothesis that chromosomal alpha-globin genes are subject to chromatin-dependent repression mechanism that prevents expression in nonerythroid cells. Our data suggest that HSV ICP0 and ICP4 either break or bypass this cellular gene silencing mechanism.

Adenovirus E1A Proteins↗
PubMed1997

A prospective study of assaults on staff by psychiatric in-patients.

This study determined the prevalence and features of assaults on staff, compared them with other aggressive incidents by psychiatric in-patients, and studied their relationship with the ward atmosphere. There were 181 physical assaults among 279 staff in two months, i.e. 389 assaults per 100 staff per year. A few patients were responsible for the majority of the assaults. Most assaults were triggered off by staff-patient interaction. About one-third of the staff were significantly psychologically shaken by the incidents. Patients were more likely to be provoked and used more severe means of aggression against staff than against other targets of aggression. There were no significant differences between the characteristics of patients who assaulted staff and those who had other targets of aggression.

Adolescent↗
PubMed1997

Studies of aggressive behaviour in schizophrenia: is there a response bias?

Of 73 patients who met selection criteria to enter into a study on aggressive behaviour in schizophrenia, 11 patients (15.1%) did not participate. The participants and non-participants were similar in age, gender ratio and proportion who had aggressive behaviour. The participants, however, had a longer duration of illness, a longer duration of current admission, were more likely to suffer from residual schizophrenia, but less likely to suffer from disorganized schizophrenia and were less severely ill than the non-participants. These results indicate the need, in studies of aggressive behaviour in schizophrenia, to consider non-response bias as a confounding variable.

Adult↗
PubMed1997

Aggressive behaviour in schizophrenia: the role of psychopathology.

OBJECTIVE: The aim of this study was to determine the psychopathological correlates of aggressive behaviour in schizophrenia. METHOD: Thirty-one aggressive patients in rehabilitation wards meeting DSM-III-R criteria for schizophrenia were compared with 31 matched non-aggressive patients in relation to their psychopathology using the Clinical Global Index (CGI), Positive and Negative Symptoms scale (PANSS) and the Montgomery-Asberg Depression Rating Scale. RESULTS: The aggressive group had significantly higher CGI, positive symptom, negative symptom, general psychopathology and total PANSS scores than the non-aggressive group. The two groups could be distinguished by three sets of symptoms: symptoms with verbal or/and physical aggression as part of their definition; symptoms suggesting frontal lobe impairment; and excitement. The two groups did not differ in their level of depressive symptomatology. CONCLUSIONS: The aggressive group were overall more ill than the non-aggressive group, and the former could be distinguished from the latter by certain aspects of their psychopathology.

Adult↗
PubMed1997

Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.

We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.

Administration, Sublingual↗
PubMed1996

Complexes of myosin subfragment-1 with adenosine diphosphate and phosphate analogs: probes of active site and protein conformation.

Previous work has revealed phosphate-dependent differences in the complexes formed from myosin subfragment-1 with adenosine diphosphate (S1.ADP) and aluminum fluoride (AlF4-) or beryllium fluoride (BeFx) [Phan and Reisler, Biophys. J., 66 (1994) A78], with the former resembling more the S1**.ADP.Pi state while the latter resembles more the S1.ATP state. In this work, the conformations of the S1.epsilon ADP.AlF4- and S1.epsilon ADP.BeFx, complexes were examined by nucleotide chase and collisional quenching experiments. epsilon ADP release from S1.epsilon ADP.AlF4- was slower than that from S1.epsilon ADP.BeFx. However, acrylamide titrations of S1.epsilon ADP.AlF4- and S1.epsilon ADP.BeFx showed little difference in nucleotide protection from quenching between the two complexes. This contrasts with the earlier observation on phosphate analog-dependent changes in the reactivity of the SH1 group on S1. To confirm phosphate-related perturbation of the SH1-SH2 sequence, emission spectra of fluorescein (IAF)-labeled SH1 and IANBD-labeled SH2 were recorded for S1 complexes with nucleotides and phosphate analogs. Considerable differences were found between the BeFx and AlF4- complexes with S1.MgADP for both SH1- and SH2-labeled proteins. These results are consistent with a recent crystallographic study of S1 complexes with ADP and phosphate analogs [Fisher et al., Biophys. J., 68 (1995) 19S] and the idea that the opening of the nucleotide cleft on S1 does not change much during ATP hydrolysis [Franks-Skiba et al., Biochemistry, 33 (1994) 12720], while significant changes in the SH1-SH2 region accompany phosphate cleavage.

Acrylamides↗
PubMed1996

Use of trephine stoma in sigmoid volvulus.

INTRODUCTION: Sigmoid volvulus is a disease of the elderly who often have severe comorbid conditions that increase their operative risk and limit treatment options. Conservative treatment with decompression via sigmoidoscopy with rectal tube placement has high success and recurrence rates. Surgical resection with primary anastomosis is the treatment of choice when decompression fails or if the volvulus recurs. Unfortunately, perioperative complications are frequent. Moreover, many patients with sigmoid volvulus are bedridden or incontinent of stool and do not benefit from extensive resection and maintenance of bowel continuity. METHODS: Twelve debilitated patients with sigmoid volvulus determined preoperatively to be poor candidates for laparotomy and reanastomosis were treated with a trephine stoma. Initially, each patient had decompression via rigid sigmoidoscopy and rectal tube placement. Surgical intervention consisted of formation of a small hole (trephine) in the left lower quadrant. Through this hole, a sigmoid resection and end colostomy were performed. No midline laparotomy was required. RESULTS: Operative times and analgesia requirements were significantly decreased (P = 0.05) compared with patients who underwent formal laparotomy. Length of hospital stay, complication rates, and length of bowel resected were similar using either surgical technique. CONCLUSIONS: The trephine stoma procedure offers significantly shorter operative times, with decreased perioperative morbidity. For high operative risk or debilitated patients with sigmoid volvulus, resection with end colostomy using the trephine stoma technique is the procedure of choice.

Adult↗
PubMed1996

Aggressive behaviour and extrapyramidal side effects of neuroleptics in schizophrenia.

The objective of this study was to determine whether extrapyramidal side effects of neuroleptics are associated with aggressive behaviour in schizophrenia. Thirty-one physically aggressive patients meeting DSM-III-R criteria for schizophrenia were compared with 31 matched non-aggressive patients in relation to their extrapyramidal side effects, including drug-induced parkinsonian (DIP) symptoms, akathisia and tardive dyskinesia. The aggressive group had significantly more severe DIP side effects than the non-aggressive group, but the association disappeared when level of psychopathology was controlled for. The aggressive group had more severe akathisia than the non-aggressive group, but the difference was not statistically significant. The two groups did not suffer in the severity of tardive dyskinesia. There was no significant, independent effect of extrapyramidal symptoms on aggressive behaviour in our sample of schizophrenic patients.

Adolescent↗
PubMed1996

A prospective study of aggression among psychiatric patients in rehabilitation wards.

OBJECTIVE: The aim of the study was to determine, among patients in rehabilitation wards, the prevalence and nature of aggressive behaviour and the relationship between aggressive behaviour and patient characteristics and ward factors. METHOD: The aggressive behaviour of all 220 inpatients within the rehabilitation program of a large psychiatric hospital in Victoria was assessed using the Staff Observation Aggression Scale. RESULTS: Physical assaults occurred at a rate of 97.6 per 100 patients per year. About 40% of all incidents appeared to be unprovoked. Most physical incidents involved use of body parts and use of a weapon was uncommon. Aggression was most often directed at a staff member. Serious injury was rare. Aggressive behaviour was correlated with gender and duration of admission for the whole sample; however, there were different correlates of aggressive behaviour for different ward populations and different types of aggression. As for ward variables, time of day but not patient/staffing level was associated with aggressive behaviour. CONCLUSIONS: There was a high rate of aggressive behaviour among patients in rehabilitation wards; this should be taken into consideration in the planning of their community placement. The findings also caution against aggregating different ward populations and types of aggressive behaviour for research.

Adult↗
PubMed1995

Structure and function of C-CAM1: effects of the cytoplasmic domain on cell aggregation.

C-CAMs are epithelial cell-adhesion molecules of the immunoglobulin supergene family with sequences highly homologous to carcinoembryonic antigen (CEA). C-CAMs and their human homologues, biliary glycoproteins, are unique among the CEA-family proteins in that they have cytoplasmic domains. Furthermore, alternative splicing generates C-CAM isoforms with different cytoplasmic domains, suggesting that the cytoplasmic domains of C-CAM may play important roles in regulating the function or functions of C-CAM. By using both sense and antisense approaches, we have shown that C-CAM1 is a tumour suppressor in prostate carcinogenesis. This observation raises the possibility that the cytoplasmic domain of C-CAM1 may be involved in signal transduction or interaction with cytoskeletal elements to elicit the tumour suppressor function. The cytoplasmic domain of C-CAM1 contains several potential phosphorylation sites, including putative consensus sequences for cyclic AMP-dependent kinase and tyrosine kinase. One of the potential tyrosine phosphorylation sites is located within the antigen-receptor homology (ARH) domain. The ARH domain of the membrane-bound IgM molecule is necessary for signal transduction in B-cells. These structural features suggest that the cytoplasmic domain of C-CAM1 may be important for signal transduction. To test this possibility, we generated several site-directed C-CAM1 mutants and tested their ability to support adhesion and their abilities to be phosphorylated in vivo. Results from these studies revealed that Tyr-488 is phosphorylated in vivo. However, replacing this tyrosine with phenylalanine did not significantly compromise its adhesion function. Similarly, Ser and Thr residues are phosphorylated in vivo, but deletion of the potential cyclic AMP-dependent kinase site did not significantly reduce the adhesion function. These results suggest that the kinase phosphorylation sites in the cytoplasmic domain of C-CAM1 are not required for the adhesion function. However, these phosphorylation sites are probably involved in the regulation of C-CAM-mediated signal transduction. Thus, there are probably distinct structural requirements for the adhesion and the signal transduction functions of C-CAM. Incidentally, a C-CAM1 deletion mutant containing a 10-amino-acid cytoplasmic domain was able to support adhesion activity. This is in contrast to our previous finding that a C-CAM isoform, C-CAM3, with a 6-amino-acid cytoplasmic domain could not support cell adhesion. This result indicates that the extra four amino acids, which are absent in C-CAM3 and contain a potential Ser/Thr phosphorylation site, are important for the adhesion function.

Adenosine Triphosphatases↗