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Biomedical subjects

A W Chan

Publications and source records attributed to A W Chan.

At least 19 recordsLinked to original sources
PubMed1997

Impairment of mitochondrial respiration and electron transport chain enzymes during cocaine-induced hepatic injury.

Morphological and biochemical changes in mitochondrial have been reported early in the course of cocaine-induced hepatotoxicity. This study was designed to examine the effects of repeated cocaine exposure in vivo on mitochondrial respiration, activities of respiratory chain enzymes, and lipid peroxide measures in liver. Male Sprague-Dawley rats were exposed to cocaine (5 i.p. injections of 25 mg/kg; 3-day period). Blood and liver samples were taken, and hepatic mitochondria were isolated by differential centrifugation. The cocaine-treated rats developed oxidative stress in hepatic mitochondria as evidenced by a significant increase in malonaldialdehyde (MDA; 52%; p < 0.0001) and a decreased glutathione (GSH; 22%; p < 0.0003). Blood aspartate aminotransferase (AST) and glutathione s-transferase (GST) levels in cocaine groups were significantly elevated (2.6 and 3.2 fold, respectively; p < 0.0001 for both). Cocaine caused a decrease in state-3 respiration and respiratory control ratio (RCR) ratio when exposed to site I and II substrates; these changes were parallelled by a decrease in complex I (22%; p < 0.003), succinate cytochrome c reductase (27%; p < 0.004), and complex IV (24%; p < 0.003). In conclusion, functional abnormalities of hepatic mitochondria accompany lipid peroxidation caused by cocaine, supporting the hypothesis that the mitochondria is one of the major intracellular targets of cocaine hepatotoxicity.

Animals↗
PubMed1997

Cocaine-induced increase of Mn-SOD in adult rat liver cells.

Cultured adult rat liver cells (non-induced) were exposed to two different concentrations (2 microg/ml and 4 microg/ml) of cocaine-HCI for 1-3 hours. Cocaine-treated rat liver cells showed a significant increase in manganese superoxide dismutase (Mn-SOD) activity with time. Coinciding the rise in Mn-SOD activity was the Mn-SOD mRNA transcript, which also demonstrated a time-dependent elevation in its level (p<0.005). At the end of 1 and 3 hr. of cocaine exposure, the increase in Mn-SOD activity was 23% (p<0.05) and 39% (p<0.005), respectively. In contrast, activities of catalase (CAT) and glutathione peroxidase (GSH-px) were significantly diminished. Induction of Mn-SOD mRNA by cocaine (4 microg/ml) was inhibited by actinomycin D (4 microM), revealing that the up regulation of Mn-SOD involved transcriptional activation. The increase in Mn-SOD was accompanied by a decrease in liver cell integrity, indicated by increased lactate dehydrogenase (LDH) release by rat liver cells. These results suggest that antioxidant enzymes may play a critical role in cocaine-induced liver injury.

Animals↗
PubMed1997

The management of acute myocardial infarction in a patient with polycythemia rubra vera during the thrombolytic era--does it make a difference?

A 42-year-old man presented with acute anterior myocardial infarction and hemoglobin of 248 g/L. Laboratory studies suggested the diagnosis of polycythemia rubra vera (PRV). Management of this condition with acetylsalisylic acid, heparin, warfarin and phlebotomy constitutes a therapeutic dilemma. This case also brings up the question of the appropriateness of thrombolysis and angioplasty in the treatment of myocardial infarction in the presence of PRV. Due to the rarity of this hematological disease, a call for international collaboration for assessing the efficacy and safety of these treatment modalities is recommended.

Adult↗
PubMed1997

Management of unstable coronary syndromes in patients with previous coronary artery bypass grafts following coronary angiography.

OBJECTIVE: To characterize patients who had undergone previous coronary artery bypass grafting (CABG) and who were admitted for coronary angiography for unstable coronary syndromes, to determine the long-term therapy selected for these patients and to assess the outcomes of the intervention. DESIGN: Descriptive retrospective study. SETTING: A university-affiliated tertiary care institution. PATIENTS: A total of 129 patients with 1 previous CABG who underwent coronary angiography for myocardial infarction or unstable angina in 1991. OUTCOME MEASURES: Information regarding initial CABG, indications for cardiac angiography, cardiovascular risk factors, ultimate treatment selected and outcomes at 1 year were abstracted from patients' charts, and outcomes at 1 year were also determined by a patient survey. RESULTS: Seventy-six patients (59%) were given drug therapy, 28 patients (22%) were treated with angioplasty, and 25 (19%) underwent repeat surgery. During their index admissions, of patients given drug therapy, 4 (5.3%) died from myocardial infarction (MI) and 42 (55%) were discharged without complications; of those undergoing angioplasty, all except 2 were treated successfully (major procedural complications included nonfatal MI in 1 patient [4%] and nonfatal ventricular arrhythmia in 1 patient [4%], as well, reocclusion of the lesions occurred before discharge in 2 patients [7%]); of those undergoing repeat surgery, almost all patients (96%) were discharged, except 1 who died from MI during the postoperative period (there were no procedural complications, but early complications included nonfatal MI in 2 patients [8%], angina in 2 [8%] and nonfatal arrhythmias in 11 [44%]). Eighty-seven patients (67%) were available for follow-up at 1 year. Of the patients given drug therapy, 3 (6.4%) had died, 14 (30%) had recurrent anginal episodes and 5 (11%) required either angioplasty or CABG. Of the patients who initially received angioplasty, 15 (63%) had recurrent angina but none died, 12 (50%) underwent repeat angioplasty and 2 (8.3%) required repeat CABG. No patients who received repeat surgery died or required further surgery or angioplasty. Three of these patients (19%) had recurrent angina within the first year. Patients in this category also enjoyed a greater degree of symptomatic improvement of coronary artery disease. CONCLUSIONS: Patients who had a previous CABG and subsequently presented with MI were more likely to be given conservative drug therapy than those who presented with unstable angina. At 1-year follow-up, recurrent angina occurred more often in the patients treated by angioplasty, less often in patients given drug therapy and least in those who underwent repeat bypass grafting. Restenosis remained a problem, and about 50% of patients treated with angioplasty (without intracoronary stenting) required a second angioplasty within the first year. Patients who were candidates for repeat CABG enjoyed greater symptomatic improvement within the first year.

Angina, Unstable↗
PubMed1996

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Acrylamides↗
PubMed1996

Trypanosomal nucleoside hydrolase. Resonance Raman spectroscopy of a transition-state inhibitor complex.

The transition state for hydrolysis of the N-ribosidic bond of inosine by nucleoside hydrolase has oxocarbenium character and a protonated leaving group hypoxanthine with an sp2-hybridized C1' of the ribosyl [Horenstein, B. A., Parkin, D. W., Estupinan, B., & Schramm, V. L. (1991) Biochemistry 30, 10788-10795]. These features are incorporated into N-(p-nitrophenyl)-D-riboamidrazone, a transition state analogue which binds with a dissociation constant of 2 nM [Boutellier, M., Horenstein, B. A., Semenyaka, A., Schramm, V. L., & Ganem, B. (1994) Biochemistry 33, 3994-4000]. Resonance Raman and ultraviolet-visible absorbance spectroscopy has established that the inhibitor binds as the neutral, zwitterionic species. The enzyme stabilizes a specific resonance state characterized by the quinonoid form of the p-nitrophenyl group with evidence for ion pairing at the nitro group. Incorporation of 15N into a specific position of the amidrazone reveals that the exo-ribosyl nitrogen bonded to the C1' position carries the proton while that bonded to the p-nitrophenyl carbon is unprotonated. This tautomer carries a distributed positive charge centered at the position analogous to C1' of the ribosyl group at the transition state. The molecular electrostatic potentials for the substrate inosine, the transition state, and the transition state inhibitor are compared at the van der Waals surface of the molecules. The tautomer of the inhibitor bound to the enzyme bears a striking electrostatic resemblance to the transition state determined by kinetic isotope effect analysis. The spectral and resonance Raman properties of free and enzyme-bound inhibitor have permitted tautomeric assignment of these species and establish that the enzyme substantially changes the electronic distribution of the bound inhibitor toward that of the enzyme-stabilized transition state.

Animals↗
PubMed1996

Detection of alcohol problems in primary care outpatients under different conditions.

Outpatients from two primary care clinics in a county hospital were screened for alcohol problems under three conditions. The objective was to determine whether patients would report more drinking and alcohol-related problems if self-report information was gathered in a research setting and/or if patients knew that their doctors would not be informed about their self-reports. The data indicate that patients' self-reports of alcohol consumption or problems were not affected by their knowledge that doctors would know their responses, and that interviews conducted in medical settings did not corrupt self-report data.

Adult↗
PubMed1996

Prediction of relative potency of ketone protease inhibitors using molecular orbital theory.

Molecular orbital calculations were carried out on a series of model ketonic protease inhibitors. A comparison of the LUMO energy of the ketones in a variety of model heterocyclic ketone protease inhibitors shows a correlation with the electrophilicity of the carbonyl, and the sigma 1 experimental data. It is also observed that the more negative charge on the nitrogen atom in the heterocyclic ring the greater its potential as a hydrogen bond acceptor. The results of this study provide a simple means of predicting relative inhibitor potency and is therefore of use both to medicinal chemists designing protease inhibitors and in QSAR studies.

Algorithms↗
PubMed1996

An in vitro comparison of the Excalibur handpiece and hand instrumentation in curved root canals.

Root canal preparation may be the most technique-sensitive and labor-intensive procedure in endodontic therapy. Many automatic handpieces and machine-driven devices have been marketed to expedite this procedure. Excalibur is one such handpiece. The purpose of this study was to compare the Excalibur hand piece with traditional K-files for their effectiveness in shaping curved root canals. A total of 24 standardized canals in extracted human mandibular molars were randomly divided into two groups. They were instrumented either with Excalibur according to the manufacturer's instructions or manually using the step-down technique. The cross-sectional shapes of the root canal at the apical, midroot, and coronal levels were digitized before and after instrumentation. Image analyzer software was used to compare the images. The results showed that the methods removed similar amount of dentin at all three levels. Although the Excalibur handpiece had a slight tendency to straighten the canal more than hand instrumentation, the difference was not significant. Strip-perforation occurred in three specimens in the Excalibur group, but none in the manual group. There was no separation of instrument throughout the experiment.

Dental High-Speed Equipment↗
PubMed1996

Cocaine-induced peroxidative stress in rat liver: antioxidant enzymes and mitochondria.

This study investigated how the cocaine-induced lipid peroxidation affected liver antioxidant enzymes and mitochondria. Acute cocaine (40 mg/kg) injection produced a significant, time-dependent increase in manganese-superoxide dismutase (Mn/SOD) activity and cellular thiobarbuturic acid reactive substances (TBARS), but activities of glutathione peroxidase and catalase were reduced significantly. These changes coincided with increased production of reactive oxygen species by mitochondria and decreased cellular ATP and glutathione. Binge cocaine (25 mg/kg; 5 injections in 3 days) significantly increased TBARS and conjugated dienes, but decreased ATP and glutathione. Accumulation of TBARS and reduction of glutathione was seen in mitochondria. Activities and mRNA of Mn/SOD and copper-zinc-superoxide dismutase were significantly elevated, but mRNA and activities of glutathione peroxidase and catalase were decreased in cocaine-treated rats. Cocaine (binge model) produced scattered liver necrosis (20%) and compromised cell integrity. This is the first report demonstrating cocaine-induced liver necrosis in rats. Pretreatment (acute model) with dimethylaminoethyl-2,2-diphenylvalerate, inhibitor of cocaine bioactivation, curtailed in part the generation of reactive oxygen species by mitochondrial fraction. Dimethylaminoethyl-2,2-diphenylvalerate also prevented the increase of TBARS and Mn/SOD. The results suggest that elevated levels of Mn/SOD and copper-zinc-superoxide dismutase, without a concomitant increase in glutathione peroxidase, catalase and glutathione s-transferase, may have contributed to cocaine-induced cellular and mitochondrial peroxidative stress. Reactive metabolites of cocaine N-oxidative metabolism may be responsible for the cocaine-induced oxidative stress and liver necrosis.

Animals↗
PubMed1996

Thoracoscopic resection of oesophageal diverticulum: a case report.

The introduction of video-assisted surgery has revolutionized thoracic surgery. The main attraction is the avoidance of a large thoracotomy incision and its associated morbidity. We present the case of a 55-year-old woman with an oesophageal diverticulum presenting with troublesome dysphagia. A thoracoscopic assisted oesophageal diverticulectomy was performed. Post-operative recovery was uneventful, and only two doses of intramuscular opiate analgesic were required. The patient remained asymptomatic at a follow-up of 3 months.

Diverticulum, Esophageal↗
PubMed1996

Utilization of antidiabetic drugs in Hong Kong: relation to the common occurrence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions and the relative prevalence of NIDDM.

Antidiabetic drug-induced hypoglycemia as a cause of acute medical admissions is more common in Hong Kong (1.7%) than in other countries (0.1-0.5%). To determine if this higher incidence may be related to the frequent use of some sulphonylureas, we have studied the overall prescribing patterns in the public sector in 1994 by reviewing the utilization of antidiabetic drugs in the general out-patient/general practice clinics (GOPD) and Hospital Authority public hospitals and affiliated specialist clinics (HA). The vast majority of patients (90.5%) receiving antidiabetic treatment were taking sulphonylureas and/or metformin, confirming that diabetes mellitus in Hong Kong is predominantly of the noninsulin-dependent type. The GOPD and the HA each accounted for approximately half of the sulphonylureas (55% vs 45%) and metformin (43% vs 57%) prescribed. Glibenclamide (84.9% vs 79.1%, 83.7% overall) and gliclazide (12.8% vs 16.6%, 14.5% overall) were the 2 most frequently used sulphonylureas. Only 9.5% of patients on antidiabetic drugs were receiving insulin and 92% of this was prescribed by the HA. For comparison, Singapore has a similar prevalence of diabetes mellitus but a much lower incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions (0.5%). Tolbutamide was the most frequently used there sulphonylurea (66.6-72.2%) with glibenclamide only contributing 20.8-28.6%. Thus, the predominant use of glibenclamide in Hong Kong may contribute to the high incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions.

Acute Disease↗
PubMed1996

Delayed diagnosis of diltiazem overdose in a patient presenting with thrombosis of femoral artery.

Previous cases of diltiazem overdose described patients who presented with hypotension, heart block, bradycardia, or ultimately death. This report concerns an elderly patient presenting to the emergency room with hypotension, an ischemic leg and confusion. He underwent an emergency thrombectomy of the femoral artery. He had severe lactic acidosis, persistent hypotension requiring prolonged inotropic support and difficulty being weaned from the ventilator after the operation. Subsequent investigations confirmed that he attempted suicide by taking an unknown quantity of diltiazem. Because diltiazem has been increasingly prescribed to treat various cardiovascular disorders, overdose may become a more common problem. A high index of suspicion is required to ensure prompt diagnosis and appropriate treatment when patients taking this medication present with sudden circulatory collapse. A guide to the management of diltiazem overdose is provided.

Bradycardia↗
PubMed1996

Delayed diagnosis of acute rheumatic fever in adults: a forgotten cause of febrile polyarthritis.

Acute rheumatic fever is a nonsuppurative sequela of upper respiratory tract infection with group A streptococci. We describe our recent experience with the diagnosis and management of 3 cases of acute rheumatic fever to highlight the delays that may arise in the diagnosis of this condition. In adults, febrile polyarthritis is the most common presentation of acute rheumatic fever. Increased awareness on the part of the physician is necessary to ensure both prompt and accurate diagnosis of this cause of febrile polyarthritis.

Adult↗
PubMed1995

A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells.

We have identified a novel cDNA encoding a protein (named TX) with > 50% overall sequence identity with the interleukin-1 beta converting enzyme (ICE) and approximately 30% sequence identity with the ICE homologs NEDD-2/ICH-1L and CED-3. A computer homology model of TX was constructed based on the X-ray coordinates of the ICE crystal recently published. This model suggests that TX is a cysteine protease, with the P1 aspartic acid substrate specificity retained. Transfection experiments demonstrate that TX is a protease which is able to cleave itself and the p30 ICE precursor, but not to generate mature IL-1 beta from pro-IL-1 beta. In addition, this protein induces apoptosis in transfected COS cells. TX therefore delineates a new member of the growing Ice/ced-3 gene family coding for proteases with cytokine processing activity or involved in programmed cell death.

Amino Acid Sequence↗
PubMed1995

Substrate recognition by ribosome-inactivating protein studied by molecular modeling and molecular electrostatic potentials.

A computer model of dianthin 30, a type 1 ribosome-inactivating protein (RIP), is constructed by homology modeling using two known X-ray structures; a type 1 RIP, pokeweed antiviral protein (PAP), and chain A of a type 2 RIP, ricin. The 3D structure is refined by molecular dynamics and its binding site compared with those of PAP and ricin using molecular electrostatic potential mapping. The differences in the maps obtained clearly show how, despite the similarity of the topology of the binding site, differences in electrostatic potential can account for the experimentally observed differences in substrate recognition and binding. This demonstrates the potential of these techniques for guiding further experimental analyses.

Amino Acid Sequence↗
PubMed1995

Can the Hospital Anxiety and Depression (HAD) Scale be used on Chinese elderly in general practice?

A study was carried out in a general practice in Hong Kong to find out if the Hospital Anxiety and Depression (HAD) Scale could be used to detect psychological problems in Chinese elderly. The HAD Scale was translated into Cantonese and administered by an interviewer to 298 Chinese aged 60 or above before their doctor consultations. The acceptance rate of the Scale was 96% and each interview took only 5-10 min to complete. All 298 elderly understood and completed the HAD Scale. Validation of the results of the HAD Scale by the Clinical Interview Schedule (CIS) was done on a random sample of 100 elderly. Relative operating characteristic (ROC) analysis showed that the optimal cut-off points of the HAD Scale was a depression score of 6 and an anxiety score of 3. The sensitivity was 80%, specificity was 90%, OMR (overall misclassification rate) was 12%, positive predictive value was 67% and negative predictive value was 95%. Thirty-six per cent of the elderly had scores above these cut-off points. More females than males had high anxiety scores. Nearly half of those with positive HAD scores were not known to have any psychological illness. The HAD Scale has great potential to be used as a screening instrument for psychological illnesses in Cantonese-speaking Chinese elderly all over the world.

Age Factors↗