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Biomedical subjects

W Ling

Publications and source records attributed to W Ling.

At least 19 recordsLinked to original sources

LAAM maintenance vs methadone maintenance for heroin dependence.

BACKGROUND: LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing. LAAM is not as widely available internationally as methadone, and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation. OBJECTIVES: To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence. SEARCH STRATEGY: We searched MEDLINE (January 1966 to August 2000), PsycINFO (1887 to August 2000), EMBASE (January 1985 to August 2000), and the Cochrane Controlled Trials Register (Issue 2 2000). In addition we hand searched NIDA monographs until August 2000 and searched reference lists of articles. SELECTION CRITERIA: All randomised controlled trials, controlled clinical trials and controlled prospective studies comparing LAAM and methadone maintenance for the treatment of heroin dependence and measuring outcomes of efficacy or acceptability were included. DATA COLLECTION AND ANALYSIS: Data on retention in treatment, heroin use, side-effects and mortality were collected by two reviewers independently. A meta-analysis was performed using RevMan. Discrepancies were resolved by consensus. MAIN RESULTS: Eighteen studies, (15 RCTs, 3 Controlled prospective studies) met the inclusion criteria for the review. Three were excluded from the meta-analysis due to lack of data on retention, heroin use or mortality. Cessation of allocated medication (11 studies, 1473 participants) was greater with LAAM than with methadone, (RR 1.36, 95%CI 1.07-1.73, p=0.001, NNT=7.7 (or 8)). Non-abstinence was less with LAAM (5 studies, 983 participants; RR 0.81, 95%CI 0.72-0.91, p=0.0003, NNT=9.1 (or 10)). In 10 studies (1441 participants) there were 6 deaths from a range of causes, 5 in participants assigned to LAAM (RR 2.28 (95%CI 0.59-8.9, p=0.2). other relevant outcomes, such as quality of life and criminal activity could not be analysed because of lack of information in the primary studies. REVIEWER'S CONCLUSIONS: LAAM appears more effective than methadone at reducing heroin use. More LAAM patients than methadone ceased their allocated medication during the studies, but many transferred to methadone and so the significance of this is unclear. There was no difference in safety observed, although there was not enough evidence to comment on uncommon adverse events.

Clinical Trials as Topic↗

Risperidone pre-treatment reduces the euphoric effects of experimentally administered cocaine.

Pre-clinical research implicates dopaminergic neurotransmission as critical in producing the effects of stimulants. Previous stimulant challenge studies using volunteers treated with dopaminergic antagonists have generally failed to demonstrate reduction of subjective effects. We performed this study to determine whether repeated dosing with risperidone reduced the subjective effects of experimentally administered cocaine. Nine non-treatment seeking hospitalized cocaine-dependent volunteers received 40 mg cocaine IV before and following 5 days of treatment with risperidone, 2 mg per day. Risperidone pre-treatment reduced the self-rated 'high' produced by cocaine. Repeated, rather than single, dosing with a D2 antagonist may be necessary to reduce the subjective effects produced by cocaine. The degree of D2 receptor blockade produced by risperidone appears to be greater than the reduction in euphoric effects produced by cocaine, suggesting that mechanisms other than those involving D2 receptors may be important in drug-induced euphoria.

Adult↗

Pain intolerance in opioid-maintained former opiate addicts: effect of long-acting maintenance agent.

Patients on methadone maintenance therapy are relatively intolerant of pain, a finding hypothesized to reflect a hyperalgesic state induced by chronic opioid administration. To explore if the intrinsic activity of the opioid maintenance agent might affect expression of hyperalgesia in this population, withdrawal latency for cold-pressor (CP) pain was compared between small groups of methadone-maintained (n = 18), buprenorphine-maintained (n = 18), and matched control (n = 18) subjects. The opioid-maintained groups had equal and significantly shorter withdrawal latencies than controls, however it is possible that high rates of continued illicit opioid use precluded finding differences between methadone and buprenorphine groups. Differential effects of maintenance agent were found for the few subjects without illicit opioid use, such that withdrawal latencies for methadone-maintained (n = 5) were less than for buprenorphine-maintained (n = 7) which were less than controls (n = 18). Diminished pain tolerance in patients receiving opioid maintenance treatment has significant clinical implications. More research is needed to determine if buprenorphine offers advantages over methadone in this regard.

Adult↗

Hyperalgesic responses in methadone maintenance patients.

Opioid substitution treatment for dependence may alter sensitivity to pain. Previous studies on pain sensitivity in methadone maintenance patients have yielded contradictory results. This study compared nociceptive responses between 16 patients on stable, once daily, doses of methadone and 16 matched control subjects. Two types of nociceptive stimuli were used: (1) electrical stimulation; and (2) a cold pressor test. Two parameters were measured: detection for onset of pain, and pain tolerance. Methadone patients were tested over an inter-dosing period: at the time of trough plasma methadone concentration (0 h), and 3 h after their daily dose. Control subjects were tested twice 3 h apart. Blood samples were collected to determine plasma methadone concentration. In methadone patients, trough to peak increases in mean R-(-)- and S-(+)-methadone concentrations (118 and 138 ng/ml to 185 and 259 ng/ml, respectively) resulted in significant increases in pain detection and tolerance values for both nociceptive stimuli. Using electrical stimulation, methadone patients' pain tolerance values were lower than controls at 0 h, but higher than controls at 3 h; no significant differences in pain detection values were found. For the cold pressor test, methadone patients detected pain significantly earlier than controls at 0 h, and were also substantially less pain tolerant than controls at both 0 and 3 h. There were no significant differences in pain detection values between the two groups at 3 h. Pain tolerance to pain detection ratios for methadone patients were significantly lower than controls for the cold pressor test at 0 and 3 h, and for electrical stimulation at 0 h only. In summary, the relative pain sensitivity of methadone maintenance patients is determined by the nature of the nociceptive stimulus (e.g. cold pressor test versus electrical stimulation), the plasma methadone concentration (trough versus peak plasma concentration), and whether thresholds are determined for detection of pain or pain tolerance. Although responding to changes in plasma methadone concentration, maintenance patients are markedly hyperalgesic to pain induced by the cold pressor test.

Adult↗

Comparing stepping-in-place and gait ability in adults with and without hemiplegia.

OBJECTIVE: To determine and compare select temporal-distance measures of stepping-in-place with gait ability in 2 age-matched groups. DESIGN: Repeated measures, matched research design. SETTING: Gait laboratory and hospital outpatient unit. PARTICIPANTS: Convenience sample recruited from within the community and the outpatient unit of a local rehabilitation hospital included 30 healthy adults (age range, 58.1 +/- 10.8yr) and 30 age-matched adults with hemiplegia (age range, 58.6 +/- 10.3yr), secondary to a cerebrovascular accident. INTERVENTIONS: Subjects were videotaped in the sagittal plane performing stepping-in-place and while walking. Select temporal-distance measures obtained by manual calculations from the video recordings were determined for 3 20-second trials of each activity. MAIN OUTCOME MEASURES: Single limb support duration (SLSD) of the lower extremities (LEs) and step frequency during stepping-in-place and during gait. RESULTS: A significant difference was found between the step frequency of each activity for the adults with hemiplegia (p <.05), but not for the healthy adults. A significant difference was also found between SLSD of the same LE across activities for each group (p <.05). SLSD of each LE during each individual activity, stepping-in-place, or gait, was not significantly different for the healthy adults, indicating LE symmetry; but it was significantly different for the adults with hemiplegia (p <.05), indicating LE asymmetry. CONCLUSIONS: Stepping-in-place incorporates reciprocal, rhythmic LE movement patterns similar to gait. And, although SLSD of the LEs was different between the activities in both groups, each group showed similar LE movement patterns during each individual activity. In addition, step frequency was consistent between the activities for the healthy adults. These results seem to indicate that the reciprocal, rhythmic LE movement patterns, which are invoked during gait, may also be invoked during stepping-in-place. However, further research is needed to enhance the data related to stepping-in-place and gait ability in clinical populations.

Case-Control Studies↗

Interferon-gamma inhibits in situ expression of PDGF-beta mRNA by smooth muscle cells in injured rabbit arteries after transluminal balloon angioplasty.

OBJECTIVE: To elucidate the mechanism of interferon-gamma (IFN-gamma) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA). METHODS: A rabbit vascular restenotic model was constructed and the proliferation of intimal smooth muscle cells (SMCs) were observed by monitoring their expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor beta chain mRNA (PDGF-beta mRNA) at the indicated time points. RESULTS: IFN-gamma could significantly inhibit the expression of PCNA by intimal SMCs one week after denudation, when counting 200 intimal cells for PCNA-positive reactions with an inhibitory rate of 88.50% (P < 0.001). IFN-gamma could downregulate in situ expression of PDGF-beta mRNA by these cells as we calculated the average number of PDGF-beta mRNA positive cells per square millimetre area at x 400 magnification with reduced rates of 86.85% in 1 week group (P < 0.001), of 93.66% in 2 week group (P < 0.001) and of 52.92% in 4 week group (0.02 < P < 0.05), respectively. CONCLUSIONS: The local production of PDGF-beta by vascular intimal SMCs via an autocrine mechanism may be responsible for continuous proliferation of these cells and the formation of neointima after injury. This could be inhibited by IFN-gamma through downregulating the expression of PDGF-beta mRNA. These results provide an in vivo basis for IFN-gamma to be used clinically for the management of restenosis after percutaneous transluminal angioplasty.

Angioplasty, Balloon↗

[Effects of black and red rice on the formation of aortic plaques and blood lipids in rabbits].

In order to observe the antiatherosclerotic effects of black and red rice and to find out their mechanism, 24 New Zealand male white rabbits (average body weight 1.91 kg) were divided randomly into three groups (white rice, black rice and red rice groups). The rabbits were fed a cholesterol-enriched diet (cholesterol 5 g/kg, lard 35 g/kg) containing 300 g/kg white, black and red rice powder respectively. The rabbits were sacrificed 10 weeks later. The aorta was dissected and stained in 0.5% oilred-isopropanol solution. The plaque area and total area of aorta were measured by an automatic image analyzer. Serum lipids were determined by an automatic analyzer. The results showed that the plaque area (% of total surface) in the black and red rice groups was significantly lower than that in the white rice group (P < 0.05). Serum TG, TC, LDL-C, ApoB and ApoAI/ApoB were not significantly different among the three groups (P > 0.05). However, the concentrations of HDL-C and ApoAI were significantly higher in the black and red rice groups than those in the white groups (P < 0.05). No significant difference was found between the black and red rice groups. It is concluded that black and red rice might be effective in reducing atherosclerotic plaques on the aorta of rabbits fed a cholesterol-enriched diet. The effectiveness of black and red rice against atherosclerosis might be related to the high level of serum HDL-C and ApoAI.

Animals↗

Pain responses in methadone-maintained opioid abusers.

Providing pain management for known opioid abusers is a challenging clinical task, in part because little is known about their pain experience and analgesic requirements. This study was designed to describe pain tolerance and analgesic response in a sample of opioid addicts stabilized in methadone-maintenance (MM) treatment (n = 60) in comparison to matched nondependent control subjects (n = 60). By using a placebo-controlled, two-way factorial design, tolerance to cold-pressor (CP) pain was examined, both before and after oral administration of therapeutic doses of common opioid (hydromorphone 2 mg) and nonsteroidal anti-inflammatory (ketorolac 10 mg) analgesic agents. Results showed that MM individuals were significantly less tolerant of CP pain than control subjects, replicating previous work. Analgesic effects were significant neither for medication nor group. These data indicate that MM opioid abusers represent a pain-intolerant subset of clinical patients. Their complaints of pain should be evaluated seriously and managed aggressively.

Adult↗

Chinese implicit leadership theory.

In a 1st attempt to identify an implicit theory of leadership among Chinese people, the authors developed the Chinese Implicit Leadership Scale (CILS) in Study 1. In Study 2, they administered the CILS to 622 Chinese participants from 5 occupation groups, to explore differences in perceptions of leadership. Factor analysis yielded 4 factors of leadership: Personal Morality, Goal Efficiency, Interpersonal Competence, and Versatility. Social groups differing in age, gender, education level, and occupation rated these factors. Results showed no significant gender differences, and the underlying cause for social group differences was education level. All groups gave the highest ratings to Interpersonal Competence, reflecting the enormous importance of this factor, which is consistent with Chinese collectivist values.

Adult↗

Cognitive impairment in individuals currently using methamphetamine.

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non-users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.

Adult↗

Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death.

Apoptosis is a tightly regulated mechanism that controls the proliferation of cells in metazoans. In mammals, multiple genes are required to regulate cell death. We have employed a gene expression knockout technique to isolate cell death-related genes. One such gene, gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), is essential for tumor cell death induced by interferon-beta (IFN-beta) and retinoic acid (RA). Here, we describe the localization of GRIM-19 to human chromosome 19p13.2. This region is essential for prostate tumor suppression. Together with its death-inductive role in the IFN-retinoid-regulated pathways and the tumor-suppressive function of this locus, the data suggest that GRIM-19 may be a novel tumor suppressor.

Breast Neoplasms↗

The future of criminal violence: juveniles tried as adults.

Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population.

Adolescent↗

[Effects of ischemic preconditioning on apoptosis of hepatocytes in liver transplantation in rats].

OBJECTIVE: To evaluate the effects of ischemic preconditioning (IP) on hepatocyte apoptosis in ischemia/reperfusion injury of grafted liver and clarify its mechanism. METHODS: Orthotopic liver transplantation with cuff anastomosing method for the portal vein, suprahepatic vena cava and infrahepatic vena cava in the rats were divided into two groups: with and without IP treatment. The parameters of liver function were determined by auto-biochemical analyser. The concentrations of malondialdehyde (MDA) were measured with chromometry. The apoptotic hepatocytes in grafts liver were detected by flow cytometry combined with the in situ terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling (TUNEL) method. RESULTS: The levels of AST, ALT, LDH in the serum, and MDA and apoptotic cells in the liver were significantly increased compared with normal values after ischemia/reperfusion to the grafted liver. After IP treatment, the levels of AST, ALT, LDH, MDA and apoptotic cells were significantly decreased. CONCLUSION: IP can attenuate ischemia/reperfusion injury by alleviating lipid peroxide and decreasing apoptosis of hepatocytes.

Animals↗

Effects of selegiline pretreatment on response to experimental cocaine administration

Several medications have been reported to alter the subjective effects of experimentally administered cocaine. We studied the effects of selegiline, a monoamine oxidase B inhibitor, on the subjective effects of experimentally administered cocaine in chronically cocaine-dependent subjects. Eight subjects completed a protocol that involved repeated administrations of cocaine before and after treatment with selegiline, given in extended release form, 10 mg per day. Four days of treatment with selegiline was associated with decreased self-reported 'high' and 'stimulated' feelings after cocaine administration, measured as the area under the curve. Changes in other subjective effects were less pronounced. Selegiline pretreatment had minimal effects on the cardiovascular responses to cocaine administration.

Journal Article↗

Magnetic resonance imaging evidence of "silent" cerebrovascular toxicity in cocaine dependence.

BACKGROUND: Cocaine and its metabolites can produce vasospasm. Cocaine-dependent (CD) patients are at increased risk for stroke, and a high frequency of brain perfusion defects has been observed in clinically asymptomatic CD subjects. This is the first controlled magnetic resonance imaging (MRI) study of clinically asymptomatic CD subjects. METHODS: Two age-matched groups of male subjects (61 CD and 57 control) participated in the study. Subjects with a history of neurologic symptoms or major medical or neurologic illness, such as hypertension, diabetes, or significant head trauma, were excluded. The severity of hyperintense lesions observed on T2-weighted MRI images were rated on a 0-3-point scale by an experienced radiologist who was blind to all clinical data. Ratings of 3 were felt to be significant indicators of a possible disease process and were used in the data analysis. Three regions were separately rated: the cerebral white matter, subinsular white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Despite the exclusion criteria minimizing risk factors for cerebrovascular events, 17 of the 61 (27.9%) CD subjects and 4 of 57 (7%) of the control subjects had severe hyperintense lesions suggestive of subclinical or "silent" anoxic vascular events. Significant group differences were observed in the two white matter regions but not in the subcortical gray matter region. The risk of severe white matter lesions in the CD group increased with age, reaching 50% in the oldest age quartile (46-58 years), and this increase was not related to the number of years cocaine was used. CONCLUSIONS: The data suggest that asymptomatic CD patients are a heterogeneous population with a significantly increased age-related risk of white matter neurovascular toxicity. Premature neurovascular damage may impact treatment outcomes and, as the CD population ages, may manifest as an increased incidence of cognitive deficits.

Adult↗

Evaluation of the cushion setting on performance of a Biodex II dynamometer.

OBJECTIVES: To compare the effects of the soft cushion setting with those of the hard cushion setting of a Biodex II isokinetic dynamometer on peak velocity and peak torque with six loads at 23 preset speeds. DESIGN: Mixed within- and between-groups, repeated-measures design. SETTING: Research laboratory of a physical therapy education program. INTERVENTIONS: Each load was strapped onto the right knee attachment of the dynamometer and was dropped through a 100 degrees arc of motion five times at each preset speed using the soft and hard cushion settings. MAIN OUTCOME MEASURES: Peak velocity, peak torque, time to peak velocity, time to peak torque. RESULTS: Peak velocity was significantly influenced by the cushion setting, the weight dropped, and the preset speed. Maximal peak velocity achieved was 400 degrees/sec. Peak torque was influenced significantly by the cushion setting, the load, and the preset speed. Maximal peak torque measured was 34.99 kg-m. CONCLUSION: The rotating shaft of Biodex II dynamometer moved at a slower speed through the entire arc of motion at the soft cushion setting and often failed to achieve a constant, preset speed. Peak torque measured using the soft cushion setting was more variable and therefore questionable.

Equipment Design↗

Regulation of interferon-alpha/beta-stimulated gene expression through the gamma-activated transcriptional element.

Interferons (IFNs) stimulate gene expression to mediate their biological actions. A multimeric transcription factor consisting of STAT1, STAT2 and p48, a DNA binding protein, regulates IFN-alpha/beta stimulated gene expression. Since the cellular level of p48 is also increased by pre-treatment of cells with IFN-gamma, it is also known as ISGF3gamma. To understand how IFN-gamma regulates the expression of the p48 gene, we have previously isolated and characterized the promoter of murine p48 gene and identified a novel gamma-IFN activated transcriptional element (GATE). In this study using several mutant constructs of p48 promoter we have determined that the same element responds to IFN-alpha/beta treatment. Relatively high doses of IFN-alpha/beta compared to IFN-gamma are required for the induction of p48 promoter. This ability of IFN-alpha/beta to regulate GATE dependent gene expression is linked to the activation of a factor induced by IFN-alpha. However, IFN-gamma induces the binding of two gamma-IFN inducible factors (GIFs) to GATE. The IFN-alpha inducible GATE binding factor is not recognized by specific antibodies raised against the known IFN-regulated factors. It is likely IFN-gamma is a stronger inducer of this gene because it activates two GIFs. GATE-like elements present in hither to undefined IFN-stimulated genes may control IFN-responses in a unique manner.

Animals↗

Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.

To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence.

Adult↗