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Biomedical subjects

W Ling

Publications and source records attributed to W Ling.

At least 37 records · Page 2Linked to original sources

The effects of circumferential wrist pressure on reproduction accuracy of wrist placement in healthy young and elderly adults.

BACKGROUND: The purpose of this study was to determine the effect of circumferential wrist pressure on reproduction accuracy of wrist placement in healthy young and elderly adults. A convenience sample of 20 young adults having a mean age of 22.9 years and 20 elderly adults with a mean age of 68.2 years participated in the study. METHOD: Blindfolded subjects were asked to actively self-select a neutral wrist position (reference) and then, when signaled, to actively reproduce the previously selected position. Wrist joint reproduction accuracy was assessed under four pressure conditions: no contact, wrist contact, 10 mm Hg, and 20 mm Hg. A single axis dynamic wrist electrogoniometer measured three dependent variables: absolute, constant, and variable errors. Data were analyzed by means of multivariate analysis of variance (MANOVA) for repeated measures. RESULTS: No significant differences in reproduction accuracy under the four pressure conditions for young or elderly adults were found. CONCLUSIONS: Healthy young and elderly adults may utilize existing intrinsic feedback and central control mechanisms to achieve accuracy during a reproduction task. Some subjects in both age groups who entered into the study with high error scores benefited from circumferential pressure by possibly relying on peripheral mechanisms. Further studies are needed to determine the effect of circumferential pressure on subjects with poor reproduction performance.

Adolescent↗

Association of depressive symptoms during abstinence with the subjective high produced by cocaine.

OBJECTIVE: During early abstinence, many cocaine-dependent individuals experience symptoms such as anhedonia, craving, fatigue, insomnia, and dysphoria. While several studies have shown an association between depressive symptoms and negative treatment outcome, the reasons for this association are unclear. The authors conducted this study in order to determine the association between severity of depressive symptoms during early abstinence and subjective effects of experimentally administered cocaine. METHOD: Seventeen cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty mg of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the cocaine. The relationship between the subjective high produced by cocaine and the symptoms experienced during the 5 days of abstinence was evaluated. RESULTS: Individuals experiencing more intense depressive symptoms experienced a significantly greater high from the 40-mg cocaine infusion than individuals who did not. CONCLUSIONS: These data suggest that the severity of depressive symptoms experienced during initial abstinence is associated with the intensity of the subsequent high produced by cocaine. This finding could help explain why individuals who experience greater levels of depression-like symptoms during abstinence appear to be at greater risk for unsuccessful treatment outcome.

Adult↗

[A preliminary clinical safety evaluation of parvovirus H-1 on cancer therapy].

OBJECTIVE: To make a preliminary evaluation of parvovirus H-1 for its safety in clinical use. METHODS: In this study, clinical safety of H-1 in cancer therapy was examined using the Ames test, the mammalian cell chromosome aberration test, the micronucleus calculation of mouse bone marrow cells, the allergy test and the pyrogenicity test. RESULTS: Negative results were observed in all the tests. The mouse tolerance test showed that the tolerance limit was at least 5 x 10(11) plaque-forming units/kg weight, which was 2500 times higher than the supposed clinical dose. The H-1 host NB-324K cells were also tested using the anchorage-independent assay and the tumour formation in nude mice. Both of the assays gave negative results. CONCLUSION: All these results preliminarily showed that the H-1 was safe in cancer therapy.

Animals↗

Impaired activation of NFkappaB in T cells from a subset of renal cell carcinoma patients is mediated by inhibition of phosphorylation and degradation of the inhibitor, IkappaBalpha.

Activation of the transcription factor NFkappaB in peripheral blood T cells from patients with renal cell carcinoma (RCC) is compromised. This impaired signaling function results from a failure of RelA and c-Rel to translocate to the nucleus though normal levels of Rel proteins are present in the cytoplasm. We demonstrate here in a subset of RCC patients that the defect in NFkappaB activation is attributable to the absence of phosphorylation and degradation of the inhibitor IkappaBalpha. In patient T cells there was no stimulus dependent decrease in the cytoplasmic level of IkappaBalpha. Coimmunoprecipitation studies showed that RelA was in complex with IkappaBalpha and was not released after stimulation. Moreover, the phosphorylated form of IkappaBalpha detected in normal T cells after activation is absent in patient T cells. Additional experiments showed that soluble products from RCCs (RCC-S) can reproduce the same phenotype in T cells from healthy individuals. Supernatant fluid from cultured explants of RCC, but not normal kidney, inhibited the stimulus dependent nuclear translocation of NFkappaB without altering the cytoplasmic levels of RelA, c-Rel, and NFkappaB1. Phosphorylation and degradation of IkappaBalpha was also blocked by RCC-S. The mechanistic similarities between patient-derived T cells and normal T cells cultured with RCC-S suggest that the tumor-derived products may be the primary mediators of impaired T-cell function in this tumor system.

Biological Transport↗

Cocaine infusion increases interferon-gamma and decreases interleukin-10 in cocaine-dependent subjects.

The effects of cocaine infusion (40 mg) on interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) cytokine secretion were examined in 15 cocaine-dependent subjects. Pre- and postcocaine infusion peripheral blood mononuclear cells (PBMC), stimulated with phytohemagglutinin A, were cultured for 48 h and the cytokines in the supernatant measured by enzyme-linked immunosorbent assay. Cocaine infusion, but not saline infusion, increased IFN-gamma secretion and decreased IL-10 secretion, while, in PBMC collected simultaneously from control subjects, secretion of these cytokines was unaltered. Baseline IFN-gamma levels were lower and IL-10 levels higher in addicted subjects compared to those in control subjects. White blood cell and lymphocyte number and CD4(+) and CD8(+) counts were all increased following cocaine infusion. In vitro cocaine treatment of PBMC from addicted subjects suppressed both IL-10 and IFN-gamma secretion. These data suggest that acute cocaine administration, via both central and peripheral effects, may enhance Th1-type immune responses and inhibit Th2-type responses.

Adult↗

Contribution of behavior therapy and biofeedback to laxative therapy in the treatment of pediatric encopresis.

A model incorporating physiological, behavioral, and psychological parameters are presented to explain the maintenance and consequences of pediatric encopresis. It was hypothesized that the more comprehensive a treatment in addressing these parameters, the more efficacious it would be and the more children it would benefit. Eighty-seven children between the ages of 6 and 15 with the primary complaint of encopresis were randomly assigned to one of three treatments: (a) Intensive Medical Care (IMC), receiving enemas for disimpaction and laxatives to promote frequent bowel movements; (b) Enhanced Toilet Training (ETT), using reinforcement and scheduling to promote response to defecation urges and instruction and modeling to promote appropriate straining, along with laxatives and enemas; or (c) Biofeedback (BF), directed at relaxing the external anal sphincter during attempted defecation, along with toilet training, laxatives, and enemas. Three months following initiation of treatment, ETT and BF produced similar reductions in soiling/child (76% and 65%) that were superior (p's < .04) to IMC (21%). ETT significantly benefited more children than the other two treatments, employing fewer laxatives and fewer treatment sessions at a lower cost. Consistent with the presented model, reduction in soiling was associated with an increase in bowel movements in the toilet, reduction in parental prompting to use the toilet, and defecation pain. These results demonstrate that ETT should be used routinely with laxative therapy in the treatment of chronic encopresis.

Adolescent↗

Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial.

AIMS: To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels. DESIGN: Patients were randomized to four dosage groups and treated double-blind. SETTING: Twelve outpatient opiate maintenance treatment centers throughout the United States. PARTICIPANTS: Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment. INTERVENTION: Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session. MEASUREMENT: Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events. FINDINGS: Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids. CONCLUSIONS: The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.

Buprenorphine↗

A 3-year progress report on the implementation of LAAM in the United States.

AIMS: LAAM, a long-acting opioid agonist, was approved by the US Food and Drug Administration in 1993 for use in licensed narcotic treatment programs. These programs have the exclusive authority in the United States to dispense methadone and LAAM for the treatment of opiate dependence. The purpose of this report is to describe the course of LAAM's implementation and to document some of the factors that have influenced the time course and extent of this process. DESIGN: Narcotic treatment programs approved for LAAM use were contacted by telephone at three timepoints following the FDA approval of LAAM in 1993. FINDINGS: Regulatory hurdles have been the most significant factor in slowing the use of LAAM. Some clinics have enthusiastically moved LAAM into mainstream use with great success. At other clinics LAAM implementation has been impeded by staff resistance and management reluctance. Some specific clinical practices, such as provision of adequate dose levels and flexible dosing practices, appear to be associated with superior clinical response, but issues of staff and organizational attitude toward the new medication are probably the most important impediments to a more positive response. CONCLUSIONS: The tasks involved with introducing a new opiate agonist treatment into mainstream use in the United States are numerous and complex. Clinical policies, fiscal issues and regulatory factors must all be addressed. The introduction of LAAM into the treatment system provides some useful lessons as other new addiction pharmacotherapies are moved into mainstream use.

Female↗

Physical activity before and after exercise in women with chronic fatigue syndrome.

We measured physical activity after strenuous exercise in 20 women with chronic fatigue syndrome (CFS), compared to 20 sedentary healthy volunteers who exercised no more than once per week. Activity was measured for 2 weeks using a portable waist-worn vertical accelerometer. After the first week of activity monitoring, all participants returned for a maximal treadmill test, followed by continued activity monitoring for the second week. Five activity measures were derived from the data: (i) average activity; (ii) total activity; (iii) duration of waking day; (iv) duration; and (v) number of daily rests. A repeated measures ANCOVA was used to determine post-treadmill group differences accounting for pre-treadmill differences. There was a significant reduction in overall average activity after the treadmill test, with the greatest decrease on days 12 through 14. This reduction was accompanied by a significant increase in the duration of the waking day and number of daily rests. Thus, marked exertion does produce changes in activity, but later than self-report would suggest, and are apparently not so severe that CFS patients cannot compensate.

Adolescent↗

Interest in smoking cessation among methadone maintained outpatients.

The prevalence of cigarette smoking among opiate abusers is extremely high and tobacco related diseases are a major factor associated with morbidity and mortality for this group. Yet, many treatment providers remain reluctant to address smoking cessation with their clients due in part to the belief that substance abusers are not interested in quitting smoking. The present study examined self-reported interest in smoking cessation among methadone maintenance clients (N = 120) in four clinics in Los Angeles. Fifty-eight percent of subjects rated themselves as 'Somewhat' or 'Very Interested' in a smoking cessation program. Overall subjects appeared to accurately perceive the personal risks from tobacco smoking. In conclusion we find that clients in methadone maintenance treatment programs evidence a high level of interest in quitting smoking and may well be suited for a highly structured smoking cessation intervention.

Adult↗

Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene.

Oxidized low density lipoprotein (LDL) and acetyl LDL are recognized by the scavenger receptor class A type I/II (SR-AI/II) on macrophages and liver endothelial cells. Several investigators have suggested that there are additional receptors specific for oxidized LDL, but characterization of these alternate receptors for oxidized LDL and evaluation of their quantitative importance in uptake of oxidized LDL has been difficult because of overlapping ligand specificity with SR-AI/II. The purpose of this study was to determine the importance of SR-AI/II in the removal of modified LDL from the bloodstream in vivo. The clearance rate of oxidized LDL from plasma in normal mice was very rapid, and > 90% of injected dose was removed from the blood within 5 min. Clearance rates of oxidized LDL were equally high in SR-AI/II knockout mice, indicating that this receptor is not required for removal of oxidized LDL from plasma. Surprisingly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II knockout animals. The plasma clearance of radioiodinated acetyl LDL was almost fully blocked by a 50-fold excess of unlabeled acetyl LDL, but the latter only inhibited oxidized LDL clearance by approximately 5%. Both modified LDLs were cleared mostly by the liver, and there was no difference in the tissue distribution of modified LDL in control and knockout mice. Studies in isolated nonparenchymal liver cells showed that Kupffer cells accounted for most of the uptake of oxidized LDL. Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors.

Animals↗

High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II.

Oxidation of low density lipoproteins (LDL) has been implicated as a causal factor in the pathogenesis of atherosclerosis. Oxidized LDL has been found to exhibit numerous potentially atherogenic properties in vitro, including receptor-mediated uptake by macrophages. Oxidized LDL is a ligand for the class A scavenger receptor type I/II (SR-AI/II), but cross-competition studies with cultured macrophages suggested that there is an additional receptor(s) that is specific for oxidized LDL and that does not interact with acetyl LDL or other chemically modified LDL. A number of macrophage membrane proteins, including CD36, FcgammaRII-B2, scavenger receptor BI, and macrosialin/CD68, have been found to bind to oxidized LDL in vitro and have been proposed as candidate oxidized LDL receptors. However, because of overlapping ligand specificity with the SR-AI/II, it has been difficult to evaluate the relative importance of these proteins in the uptake of oxidized LDL by macrophages. In the present report, we have studied the uptake and degradation of oxidized LDL by macrophages from mice in which the SR-AI/II gene had been disrupted. The uptake of acetyl LDL was reduced by more than 80% in macrophages from scavenger receptor knockout mice, confirming that most of the uptake of acetyl LDL by macrophages can be attributed to this receptor. In contrast, the uptake of extensively oxidized LDL was reduced by only 30% and showed high affinity, saturable uptake with apparent Km of about 5 microg/ml, similar to that of the SR-AI/II. This indicates that about 70% of the uptake of oxidized LDL in macrophages is attributable to an alternate oxidized LDL receptor(s). In contrast to findings reported with CD36, mildly oxidized LDL was internalized much more slowly than extensively oxidized LDL. Unlabeled oxidized LDL, polyinosinic acid, phosphatidylserine-rich liposomes, and LDL or bovine albumin modified by fatty acid oxidation products were effective competitors for the uptake of radioiodinated oxidized LDL by macrophages from knockout mice, whereas acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors. This ligand specificity differs from that of CD36-related (class B) scavenger receptors but is similar to the reported specificity of macrosialin/CD68 in ligand blots. However, the rate of uptake of oxidized LDL by knockout macrophages was not increased by phorbol ester or in thioglycollate-elicited macrophages, both of which are expected to increase the amount of macrosialin on the cell surface. In macrophages from SR-AI/II knockout mice, ligand blots of membrane proteins with iodinated, oxidized, or acetylated LDL revealed several bands, with apparent molecular size on SDS-polyacrylamide gel electrophoresis of 60, 94, 124, and 210 kDa, but none of the bands were specific for oxidized LDL. These results provide direct evidence that a receptor other than SR-AI/II is responsible for most of the uptake of oxidized LDL in murine macrophages, but further studies are needed to identify the receptor(s) involved.

Animals↗

Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid addicts.

In a study evaluating naltrexone with either an intensive psychosocial protocol or standard community treatment for opioid dependence, 13 of 81 subjects overdosed within a 12-month period of study participation. There were four fatalities, one of which was a suicide. Among the nine nonfatal overdoses, there were four suicide attempts. Characteristics of subjects and naltrexone-taking are described.

Adult↗

Anorectal manometric examination in encopretic-constipated children.

PURPOSE: We have investigated the use of anorectal manometry to distinguish encopretic-constipated children (n = 88) from sibling controls (n = 16) and nonsibling controls (n = 11). METHODS: Study variables included manometrically determined resting and maximum voluntary anal sphincter pressure, depth and speed of rectoanal inhibitory reflex, minimum rectal volume sensation, critical distending volume for fecal urgency, rectal and anal pressure responses during attempted defecation, and ability to defecate a water-filled balloon. RESULTS: Change in anal sphincter pressure during attempted defecation (P = 0.03), gradient between rectal and sphincter pressure during attempted defecation (P = 0.02), critical distending volume for fecal urgency (P = 0.02), and ability to defecate a water-filled balloon (P = 0.05) distinguished encopretic-constipated from control children. The change in rectal pressure associated with the rectoanal inhibitory reflex just escaped significance at P = 0.07. CONCLUSIONS: Anal sphincter spasm and megacolon are pathophysiologic abnormalities associated with pediatric constipation-encopresis.

Adolescent↗

Integrating treatments for methamphetamine abuse: a psychosocial perspective.

The recent West Coast experience with increased methamphetamine use is showing signs of spreading to other parts of the US. The risk of corresponding medical and psychosocial problems has led to a call to action at the highest levels of government. The next few years will likely witness a substantial increase in treatment research on methamphetamine abuse/dependence, with particular emphasis on the development and application of novel pharmacotherapies. The evaluation of these agents presupposes that we understand the clinical syndrome resulting from chronic methamphetamine use. To establish a clear picture of the biological and psychological sequellae of methamphetamine use, we compare two cohorts (500 methamphetamine and 224 cocaine users) treated at the same outpatient clinic over the past nine years, using identical manualized treatments. The results suggest that while there are important differences in group characteristics and drug effects, the total response to treatment was quite comparable.

Adult↗

Integration of research in pharmacotherapy for addictive disease: where are we? Where are we going?

Systematic efforts by NIDA and NIAAA to develop new medications for drug and alcohol dependence have resulted in recent FDA approval of LAAM for opiate dependence, naltrexone for alcohol dependence and, more recently, a nasal spray for nicotine dependence. This article reviews the current strategies that guide these development efforts, including further examination of the interactions between potential pharmacotherapeutic agents and the drugs of abuse, the enhancement of pharmacotherapeutic efficacy with nonpharmacological interventions, and the development of more precise and meaningful measures of research outcome.

Behavior, Addictive↗

Ultrafiltration using the Amicon MPS-1 for assessing methadone plasma protein binding.

The percent of protein-free and protein-bound methadone were separated in methadone-spiked bank and artificial plasma, and in plasma samples taken from methadone-maintained patients using the Amicon MPS-1 ultrafiltration device. Following the separation procedure, protein-bound and protein-free methadone were extracted from the protein-bound and free fractions, and their respective concentrations were determined by gas chromatography and nitrogen-phosphorus detection. Eighty-five patient samples from 38 men and 10 women receiving methadone maintenance were collected and subjected to the ultrafiltration methodology. Two independent procedures demonstrated that, following the ultrafiltration process, no proteins were measurable in the filtrate. In addition, the ultrafiltration process was found to function independently of the concentration of methadone and the volume of sample, assuming the amount filtered never exceeded 40% of the original volume. In the patient samples, the %-free methadone varied sixfold across all patients. Female patients were found to have a mean +/- SD %-free methadone of 11.9 +/- 3.8% vs. 10.1 +/- 3.4% for men. Pearson correlation values suggest that steady-state protein-free methadone levels (r = 0.521) and total methadone levels (r = 0.491) rise as methadone dose is increased. Corresponding to these results, free methadone levels are highly correlated with total methadone levels (Pearson r = 0.85). The Amicon MPS-1 ultrafiltration device appears to be a reliable and relatively easy system to use for separating protein-free from protein-bound methadone, though further study is required to clarify the clinical applications of free methadone levels.

Blood Proteins↗