Biomedical subjects

A W Chan

Publications and source records attributed to A W Chan.

At least 109 records · Page 6Linked to original sources

PubMed1995

Use and abuse of benzodiazepines in Hong Kong 1990-1993--the impact of regulatory changes.

To control benzodiazepine abuse in Hong Kong, the Government's Pharmacy and Poisons Board reclassified benzodiazepines as Dangerous Drugs in October 1990. Apart from formal prescriptions, detailed records were then required for the supply and dispensing of these drugs. These regulations were applied initially only to brotizolam, triazolam and flunitrazepam, and were extended in January 1992 to include all benzodiazepines. The impact of these regulatory changes on benzodiazepine use has been studied by analyzing the sales patterns of seven benzodiazepines between 1990-1993. In 1991, the sales of flunitrazepam and triazolam fell, but the sales of five unrestricted benzodiazepines increased. In 1992-1993, the sales of all but one of the benzodiazepines fell. Comparing 1993 to 1990, the fall in sales was particularly marked for triazolam, chlordiazepoxide and flunitrazepam. A regulation requiring the use of proper prescriptions and detailed records for the supply and dispensing of benzodiazepines, appears to have curbed, at least partially, their abuse in Hong Kong.

Benzodiazepines↗

PubMed1994

The surface exclusion system of RP1: investigation of the roles of trbJ and trbK in the surface exclusion, transfer, and slow-growth phenotypes.

The contiguous trbJ and trbK genes of RP1 were cloned individually to study their effects. Surface exclusion was conferred only by trbK and only when gene dosage was high or when trbJ was also present in cis or in trans. This suggests that in the low-copy-number RP1, surface exclusion is due to a two-gene interaction in which trbK is the dominant partner. Among surface exclusion genes, trbJ is novel in yielding a periplasmic product that is also essential for conjugal transfer. This cellular location and the disturbed membrane function that accompanies TrbJ-processing probably accounts for the retarded growth caused by trbJ+ clones in Pseudomonas aeruginosa strain PAO.

Bacterial Proteins↗

PubMed1994

Influence of age on the development of rapid tolerance to ethanol.

Fischer-344 rats of three different ages (4, 13, and 25 months) were tested to determine the extent and duration of rapid tolerance to ethanol-induced hypothermia and hypnosis. There were no significant differences among groups with regard to maximal ethanol hypothermia (3.0-3.5 g/kg ethanol), nor did any of the groups display a significant change (rapid tolerance) in the maximal hypothermic response when tested with a second identical challenge 48 h later. Rapid tolerance to ethanol hypnosis was observed across groups at 48 h, utilizing two different dosing schemes. No tolerance was observed if 14 days were allowed to elapse between the initial and the test challenge. Young rats were observed to develop a greater degree of rapid tolerance than did middle-aged or old rats, using hypnosis as a measure.

Aging↗

PubMed1994

Age effects on chronic tolerance to ethanol hypnosis and hypothermia.

Male Fischer 344 rats of three different ages (young, 4 months; middle, 13 months; and old, 25 months) were tested for their hypnotic and hypothermic response to a 3.5 g/kg dose of ethanol on day 1 and after an 8-day exposure to 4.0 g/kg of ethanol administered via intragastric intubation. All three age groups displayed, to a similar extent, an increased rate of blood ethanol disappearance (metabolic tolerance) on day 10 and day 16, as compared to day 1. Both young and middle-age rats demonstrated tolerance to ethanol hypothermia, but older rats did not. The same test dose of ethanol (3.5 g/kg, IP) administered on day 16, after a 5-day interval with no ethanol, produced a hypnosis response similar to that observed on day 1 (no tolerance), but the response to ethanol hypothermia was still significantly reduced over the day 1 and day 10 value in young and middle-age rats, suggesting a persistence and intensification of tolerance to hypothermia over the 5-day rest interval. However, tolerance to ethanol hypothermia was not observed in old rats. Thus, the effects of age on the development of chronic functional tolerance were complex and depended upon the test measure used.

Aging↗

PubMed1994

Detection by the CAGE of alcoholism or heavy drinking in primary care outpatients and the general population.

There is a need to improve the diagnosis of alcoholism in clinical settings because alcoholism, particularly in its early stages, is often unrecognized in general medical practice and in hospitals. In this study the CAGE questionnaire was used to detect alcoholism or heavy drinking in three populations, namely, alcoholics in treatment (ALC), primary-care outpatients (PC), and the general population (GP). Nearly all the ALC tested positive on the CAGE (97.8%), both for current (past year) and for lifetime alcohol-related problems. Among the PC subjects, 44.8% tested positive for lifetime alcohol problems, but the prevalence decreased to 17.2% when only past-year problems were considered. Likewise, 38.3% of the GP sample tested positive for lifetime, but half of these did not meet the 1-year recency criterion. Compared to DSM-III-R criteria during the same time intervals, the sensitivity/specificity of the lifetime CAGE was 91.2%/84.0% and 76.9%/85.1% in the PC and GP, respectively. The corresponding sensitivity/specificity of the past-year CAGE was 94.4%/97.0% and 74.6%/91.6%, respectively. Thus, the CAGE is an appropriate screening test for alcohol problems in these two populations, but other confirmatory tests or interviews are necessary to eliminate false positives. There were neither gender nor racial differences in the ALC sample responses to individual CAGE questions. However, there were gender differences in the PC and GP samples, with more males responding yes to each of the questions. The gender differences probably reflected the higher prevalence of heavy drinking and alcoholism among males.

Adolescent↗

PubMed1994

Detection of alcoholism in three populations by the brief-MAST.

The brief MAST (B-MAST) questionnaire was used to detect alcoholism in three populations, namely, alcoholics in treatment, clinical outpatients, and the general population. Nearly all the alcoholics in treatment tested positive in the B-MAST (99.2%), for lifetime as well as for current (past year) alcohol-related problems. Among the clinical outpatients and general population, 35.6% and 20.2% respectively, tested positive for lifetime alcohol problems, but only 19.6% and 7.6%, respectively, tested positive for past-year alcohol problems. The sensitivity/specificity of the B-MAST (lifetime) was 64.7%/90.0% and 48.3%/96.4% in the clinical outpatients and general population, respectively. Even lower sensitivity (28.2%) was obtained when the B-MAST was used to detect past-year alcohol problems in the general population sample. The poor sensitivity of the B-MAST in the general population was probably because most of the B-MAST questions deal with severe alcohol problems, and they are not sufficiently sensitive to detect those who drank heavily but who had not yet developed these alcohol problems. Anomalous responses to the two questions about "normal drinker" and to the question about "attendance in AA meeting" also contributed (< 3%) to inflated positive B-MAST scores. There were gender differences, and to a lesser extent, racial differences (Whites versus Blacks), in the responses to individual B-MAST questions in the three subject populations, with more males than females in each group reporting more alcohol-related problems. However, there were no gender and racial differences in the average B-MAST scores among those clinical outpatients and general population subjects who tested positive.

Adult↗

PubMed1994

The prediction of diabetic neuropathic plantar foot ulceration by liquid-crystal contact thermography.

OBJECTIVE: To assess whether the development of plantar foot ulceration could be predicted from the mean plantar foot temperature (MFT), as assessed by liquid-crystal contact thermography (LCT), in patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS: Fifty patients with painful diabetic sensorimotor neuropathy were studied prospectively. Initially, 30 patients had no significant peripheral vascular disease (PVD) (ankle:brachial systolic blood pressure ratio > 1.0). LCT was used to assess the MFT from eight standard plantar sites. RESULTS: Initial MFT was higher in the patients without PVD (28.2 +/- 2.9 degrees C, mean +/- SD) than in patients with PVD (25.6 +/- 1.9 degrees C, P < 0.001) and in nondiabetic control subjects (25.7 +/- 2.1 degrees C, P < 0.001). At review, on average 3.6 (range 3.0-4.1) years later, 11 patients had died (6 of whom had PVD), and one was lost to follow-up. Six patients (seven feet) from the group without PVD had developed neuropathic plantar foot ulcers. The initial MFT was significantly higher in these seven feet (30.5 +/- 2.6 degrees C) than in the 38 feet of the 19 survivors in this group (27.8 +/- 2.3 degrees C, P < 0.01). Only one patient with PVD developed a plantar ulcer, although four required foot surgery for ischemic feet. CONCLUSIONS: LCT is a simple, inexpensive, and noninvasive method of identifying the neuropathic foot at increased risk of ulceration. Patients with high plantar foot temperatures are at increased risk of neuropathic foot ulceration. A normal or low MFT in the neuropathic foot is a marker of PVD, which confers an increased risk of ischemic foot disease.

Blood Pressure↗

PubMed1993

Identification, classification, and analysis of beta-bulges in proteins.

A beta-bulge is a region of irregularity in a beta-sheet involving two beta-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in beta-sheets were identified and classified automatically, extending the definition of beta-bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson, D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of beta-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges. Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, beta-bulges produce two main changes in the structure of a beta-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands.

Amino Acid Sequence↗

PubMed1993

High-performance liquid chromatography to assess the effect of serum storage conditions on the detection of hepatitis C virus by the polymerase chain reaction.

The effect of various serum storage conditions on the detection of hepatitis C virus (HCV) by the polymerase chain reaction (PCR) was assessed. 50 microliters aliquots of serum from four HCV PCR positive patients were subjected, in triplicate, to: (a) storage at -20 degrees C for 1, 5, 10 days; (b) storage at room temperature (RT) for 1, 2, 7 days; (c) 1, 3, 5, and 10 successive freeze-thaw cycles; (d) incubation at 37 degrees C, and 56 degrees C for 1, 3, 24 h; and (e) storage in guanidium-thiocyanate extraction buffer at RT, and 4 degrees C for 1, 5, 10 days. PCR products were detected by agarose gel electrophoresis (AGE) and quantitatively by high-performance liquid chromatography (HPLC). Only storage in extraction buffer at RT for 5-10 days and incubation at 56 degrees C for 24 h appeared to result in a loss of > or = 50% of detectable HCV PCR product. Up to 10 successive freeze-thaw cycles, storage at -20 degrees C for up to 10 days or at RT for up to 7 days, storage in extraction buffer at RT for 1 day or at 4 degrees C for up to 10 days, and incubation at 37 degrees C for up to 24 h resulted in minimal PCR signal loss. HPLC was a reproducible method of detecting and quantitating HCV PCR products, and was more sensitive than AGE.

Blood Preservation↗

PubMed1993

Age-related differences in sensitivity to alcohol in the rat.

Female F344 rats of three different ages (4, 13, and 25 months) were tested for sensitivity to the ataxic, hypothermic, and hypnotic effects of injected ethanol. Challenges with ethanol sufficient to produce similar blood alcohol concentrations (BACs) in all age groups at the time of testing were observed to produce greater ataxia in old rats (25 months > 13 months > 4 months). Old rats also were observed to recover the righting reflex at lower BACs than those present in young or middle age rats. BAC at a target rectal temperature of 36 degrees C was observed to be lower in old than in young or middle-age rats when measured as body temperature was falling after doses of 3.0 g/kg to old and 3.5 g/kg to young and middle rats. However, no differences among groups in BAC at target temperature (36 degrees C) were observed as body temperature was recovering from peak hypothermia back up to 36 degrees C. With the exception of the last observation cited, these findings appear to confirm and extend earlier reports of increased target tissue sensitivity to ethanol with advancing age in rodents.

Aging↗

PubMed1993

Use of the TWEAK test in screening for alcoholism/heavy drinking in three populations.

TWEAK is an acronym for Tolerance (T1 number of drinks to feel high; T2, number of drinks one can hold), Worry about drinking, Eye-opener (morning drinking), Amnesia (blackouts), and Cut down on drinking (K/C). In this study, two versions (T1 and T2) of the TWEAK were part of a questionnaire used to detect alcoholism or heavy alcohol intake in three populations, namely, alcoholics in treatment, patients in two outpatient clinics, and the general population. Similar to the CAGE and the 10-item brief MAST, the TWEAK identified most known alcoholics, but the TWEAK had a higher sensitivity and specificity than the CAGE and B-MAST in detecting alcoholism/heavy drinking in the clinical and general populations. Different cut-off values for tolerance (T1 and T2) are recommended for screening different populations.

Adolescent↗

PubMed1992

Neurochemical changes in rats chronically treated with a high concentration of manganese chloride.

Several neurochemical parameters were studied in brain regions of rats chronically treated with a high concentration of manganese chloride (20 mg MnCl2.4H2O per ml. of drinking water) throughout development until adulthood. Large increases in Mn accumulation were found in all brain regions (hypothalamus, +530%; striatum, +479%; other regions, +152 to +250%) of Mn-treated adult rats. In these animals, Ca levels were decreased (-20 to -46%) in cerebellum, hypothalamus, and cerebral cortex but were increased (+186%) in midbrain. Mg levels were decreased (-12 to -32%) in pons and medulla, midbrain, and cerebellum. Fe levels were increased (+95%) in striatum but were decreased (-28%) in cerebral cortex. Cu levels were increased (+43 to +100%) in pons and medulla and striatum but Zn levels were decreased (-30%) in pons and medulla. Na levels were increased (+22%) in striatum but those of K and Cl remained unchanged. Type A monoamine oxidase activities were decreased (-13 to -16%) in midbrain, striatum, and cerebral cortex, but type B monoamine oxidase activities decreased (-13%) only in hypothalamus. Acetylcholinesterase activities were increased (+20 to +22%) in striatum and cerebellum. The results are consistent with our hypothesis that chronic manganese encephalopathy not only affects brain metabolism of Mn but also that of other metals.

Acetylcholinesterase↗

PubMed1992

Changes in brain regional manganese and magnesium levels during postnatal development: modulations by chronic manganese administration.

Manganese (Mn) and magnesium (Mg) levels in hypothalamus, cerebellum, pons and medulla, striatum, midbrain, and cerebral cortex of control and Mn-treated (10 mg MnCl2.4H2O per ml of drinking water) rats during postnatal development were studied using instrumental neutron activation analysis. The age-dependent Mn accumulation showed regional variation: at day 5, this accumulation was most marked in striatum (12.05 micrograms/g wet weight) but least marked in cerebral cortex (0.85 micrograms/g wet weight). By day 10, pons and medulla, and hypothalamus were regions with, respectively, the highest (4.73 micrograms/g wet weight) and the lowest (0.52 micrograms/g wet weight) Mn levels. By contrast, brain regional Mn variations were less pronounced in weanling and adult rats. The age-dependent Mg accumulation showed regional variation at day 5, being most marked in pons and medulla (720 micrograms/g wet weight) and least marked in cerebral cortex (295 micrograms/g wet weight). Mg levels in all regions decreased after day 5; by day 120, only Mg level in cerebral cortex was lower than levels in other regions (the latter being very similar). In general, the age-related decreases in Mn and Mg levels paralleled the decreases in water content and increases in tissue weight, suggesting that the maturation of the blood-brain barrier may play important role(s) in brain Mn and Mg homeostasis. Chronic Mn-treatment from conception onwards altered the regional Mn and Mg distribution patterns during development. Our results are consistent with the hypothesis that chronic Mn toxicity exerts modulatory effects on brain regional metabolism and homeostasis of Mn and other metals during development.

Aging↗

PubMed1992

CSF enkephalins in diabetic neuropathy.

CSF methionine and leucine enkephalins were measured by high performance liquid chromatography and radioimmunoassay in diabetic patients with painful neuropathy (n = 22) and painless neuropathy (n = 5), and non-diabetic subjects with low back pain (n = 11). Wide variations in CSF enkephalin levels were found and they were often below the limit of detection (less than 0.1 pmol/l) in the diabetic and non-diabetic groups. The origin of CSF enkephalins is unknown and CSF levels may not reflect tissue concentrations. In conclusion, CSF enkephalin levels are difficult to interpret and do not provide useful information on the function of enkephalinergic pathways.

Adult↗

PubMed1992

Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy.

A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic painful neuropathy. In the controls, the mean PPT from the right hand and foot obtained on two test occasions a week apart did not differ significantly. In diabetic patients without symptomatic neuropathy, the mean PPT in the right hand and right foot were significantly higher than in the controls. The diabetic patients with painful neuropathy had clearly increased mean PPT in the right hand and foot compared with controls. Marstock thermal limen in diabetic patients with painful neuropathy correlated significantly with PPT determinations. PPT and thermal thresholds probably give comparable information on small fibre dysfunction in diabetic patients with symptomatic neuropathy. Compared with thermal threshold determinations however, the weighted needle apparatus is inexpensive, simple, and rapid to use.

Adolescent↗

PubMed1991

Effects of chronic manganese treatment on rat brain regional sodium-potassium-activated and magnesium-activated adenosine triphosphatase activities during development.

The effects of chronic manganese (Mn) treatments (1 and 10 mg MnCl2.4H2O per ml of drinking water) from conception onwards on brain regional development of sodium-potassium-activated and magnesium-activated adenosine triphosphatases (Na-K-ATPase and Mg-ATPase) were studied. The activities of these enzymes were determined in hypothalamus, cerebellum, pons and medulla, striatum, midbrain and cerebral cortex (which included the hippocampus) of Mn-treated and age-matched control rats at 5 postnatal ages. Both ATPase activities doubled in most brain regions between day 5 and day 20 postnatal. In pons and medulla, striatum, midbrain, and cerebral cortex, adult levels of both enzymatic activities were attained by day 20 postnatal. Na-K-ATPase activities transiently increased in the midbrain (+25%) at day 12 with the lower Mn dose and in the cerebral cortex (+31%) at day 20 with the higher Mn dose. With the higher Mn dose only, Mg-ATPase activities were increased in the hypothalamus (+20%) at day 12 and in the pons and medulla (+22%) at day 20 but were decreased in the pons and medulla (-20%) at day 60. Thus, only transient changes in enzymatic activities were observed despite dose-dependent increases in the brain levels of Mn resulting from the Mn treatment. A hypothesis regarding the role of early but transient changes in brain metabolism in the pathogenesis of the initial psychotic symptoms in Mn intoxication was proposed and discussed in relation to several other observations of a similar nature.

Age Factors↗

PubMed1991

Flumazenil (Ro15-1788) does not affect ethanol tolerance and dependence.

There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice were injected with either Ro15-1788 (25 mg/kg) or vehicle immediately before, 14 h or 24 h before ethanol withdrawal. Under these conditions, no attenuation of the severity of handling-induced withdrawal seizures or of withdrawal hypothermia was observed in the ethanol-dependent mice injected with Ro15-1788. Likewise, there was no abolition or attenuation of tolerance to the ataxic effects (sleep time and horizontal dowel tests) and hypothermic effects of ethanol by Ro15-1788 when the mice were tested on day 3 of ethanol withdrawal. It is concluded that Ro15-1788 (25 mg/kg) has no effect on ethanol tolerance and dependence.

Animals↗

PubMed1991

The ability of chlordiazepoxide to maintain ethanol tolerance and dependence.

Two criteria need to be satisfied in the demonstration of cross-dependence to chlordiazepoxide (CDP) in ethanol-dependent mice. These are the ability of CDP to suppress ethanol withdrawal and to maintain the dependent state. In this study, mice which had been fed chronically an ethanol diet followed by two days of CDP diet treatment had more severe CDP withdrawal signs induced by Ro15-1788 than drug-naive mice which were similarly exposed to the CDP diet treatment. The data indicate that CDP can maintain the dependent state acquired from the prior ethanol treatment. Alternatively, the prior ethanol treatment would have facilitated the development of CDP dependence, but it was not deemed likely. Three behavioral tests, namely, runway, sleep time, and drug-induced hypothermia, were used to test whether CDP could maintain the ethanol tolerance acquired from the prior ethanol treatment. The runway test showed that CDP could maintain the previously acquired ethanol tolerance. However, interpretations of the data from the sleep time and hypothermia tests are more equivocal because of factors such as peak tolerance, differential rates of development and dissipation of ethanol (or CDP) tolerance as determined by different behavioral tests.

Animals↗