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Biomedical subjects

Daniel Lin

Publications and source records attributed to Daniel Lin.

10 recordsLinked to original sources
PubMed2006

Characteristics of two alternative schizophrenia remission definitions: relationship to clinical and quality of life outcomes.

BACKGROUND: The goal of these secondary analyses of clinical trial data was to characterize clinical outcomes in patients with schizophrenia who met symptom severity or duration thresholds for two alternative definitions of remission, and to explore their relationships to improvement duration and quality of life outcomes. METHODS: Definition 1 used threshold criteria for selected PANSS items sustained over at least 6-months Definition 2 used Brief Psychiatric Rating Scale (BPRS) % change, a threshold score for the Clinical Global Improvement-Severity (CGI-S) maintained for at least 8 weeks, and threshold scores for selected BPRS items. Positive and Negative Symptom Scale (PANSS) and Quality of Life scale (QLS) total scores were pooled from 6 clinical trials. The extent to which the alternative severity thresholds from these two definitions and duration of clinical improvement were associated with different clinical and QLS outcomes was explored. Regression analysis also assessed the relative contribution of each of the components of the two definition severity thresholds to improvements in QLS Total score. RESULTS: Increases in QLS scores were greater for those patients who met either threshold criteria relative to those who met neither (p<.0001). Significantly greater improvements in QLS scores were observed for patients who met either threshold criteria at the 8-, 16- and 24-week visits relative to those who met criteria at weeks 16 and 24, or at week 24 only (p<0.001), as well as for the subset of patients who met threshold criteria at both 24 and 52 weeks relative to those who met criteria at only one of these 2 time points. Only 31% to 47% of patients meeting threshold criteria for either definition at the 8-, 16- or 24-week visits remained in remission at the 52-week visit. Among the severity threshold components analyzed, BPRS total % change from baseline was the strongest predictor of improvement in QLS scores. CONCLUSIONS: Quality of life improved most for patients who achieved severity thresholds associated with either remission criteria and who stayed improved for longer periods. Total BPRS change scores accounted for the greatest percentage of the QLS scores variance. Only a fraction of patients who meet severity criteria for either remission definition early in treatment will remain at that level of improvement within the subsequent 9-12 months.

Adolescent↗
PubMed2006

A molecular correlate to the Gleason grading system for prostate adenocarcinoma.

Adenocarcinomas of the prostate can be categorized into tumor grades based on the extent to which the cancers histologically resemble normal prostate glands. Because grades are surrogates of intrinsic tumor behavior, characterizing the molecular phenotype of grade is of potential clinical importance. To identify molecular alterations underlying prostate cancer grades, we used microdissection to obtain specific cohorts of cancer cells corresponding to the most common Gleason patterns (patterns 3, 4, and 5) from 29 radical prostatectomy samples. We paired each cancer sample with matched benign lumenal prostate epithelial cells and profiled transcript abundance levels by microarray analysis. We identified an 86-gene model capable of distinguishing low-grade (pattern 3) from high-grade (patterns 4 and 5) cancers. This model performed with 76% accuracy when applied to an independent set of 30 primary prostate carcinomas. Using tissue microarrays comprising >800 prostate samples, we confirmed a significant association between high levels of monoamine oxidase A expression and poorly differentiated cancers by immunohistochemistry. We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17 beta4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively. The altered expression of these genes provides functional insights into grade-associated features of therapy resistance and tissue invasion. Furthermore, in identifying a profile of 86 genes that distinguish high- from low-grade carcinomas, we have generated a set of potential targets for modulating the development and progression of the lethal prostate cancer phenotype.

Adenocarcinoma↗
PubMed2006

Influence of sub-syndromal symptoms after remission from manic or mixed episodes.

BACKGROUND: Sub-syndromal symptoms in bipolar disorder impair functioning and diminish quality of life. AIMS: To examine factors associated with time spent with sub-syndromal symptoms and to characterise how these symptoms influence outcomes. METHOD: In a double-blind randomised maintenance trial, patients received either olanzapine or lithium monotherapy for 1 year. Stepwise logistic regression models were used to identify factors that were significant predictors of percentage time spent with sub-syndromal symptoms. The presence of sub-syndromal symptoms during the first 8 weeks was examined as a predictor of subsequent relapse. RESULTS: Presence of sub-syndromal depressive symptoms during the first 8 weeks significantly increased the likelihood of depressive relapse (relative risk 4.67, P<0.001). Patients with psychotic features and those with a greater number of previous depressive episodes were more likely to experience sub-syndromal depressive symptoms (RR=2.51, P<0.001 and RR=2.35, P=0.03 respectively). CONCLUSIONS: These findings help to identify patients at increased risk of affective relapse and suggest that appropriate therapeutic interventions should be considered even when syndromal-level symptoms are absent.

Adult↗
PubMed2006

Polytherapy in bipolar disorder.

Bipolar disorder is a life-long condition that is associated with frequent recurrence/relapse of symptoms. Although putative mood stabilisers, such as lithium, are considered to improve the natural course of bipolar disorder, complete long-term remission is rarely achieved. In order to effectively control mood symptoms and to reduce relapse, clinicians often use polypharmacy to treat patients with bipolar disorder. In this article, we examine the recent literature on treatment strategies in bipolar disorder to determine if combination treatments provide additional benefit over monotherapy for the management of various phases of bipolar disorder. The evidence suggests that for acute mania a combination of lithium or valproate and an atypical antipsychotic is the most effective approach, with approximately 20% more patients responding to the combination than to monotherapy with any antimanic agent. Few studies have examined the use of combination therapy in comparison to monotherapy for bipolar depression. The limited evidence suggests that lithium plus an antidepressant appears to be more effective than lithium alone in those with lower serum lithium concentrations. Similarly, the combination of olanzapine plus fluoxetine is more effective than olanzapine alone. There is consensus that antidepressant monotherapy is not appropriate because of concerns of a manic switch, but monotherapy with lithium or lamotrigine may be adequate for mild to moderate bipolar depression. For maintenance treatment, commonly used agents, such as lithium, valproate or olanzapine appear to be most effective in preventing manic relapses, whereas lamotrigine is more effective in preventing depressive relapses. As a result of these findings, it makes intuitive sense to combine lamotrigine with lithium, valproate or an atypical antipsychotic to achieve better mood stability. However, the efficacy and safety of such combinations have not been systematically compared with monotherapy. Preliminary studies suggest that lithium plus valproate may be more effective than lithium alone in preventing affective relapses. Similarly, the combination of lithium or valproate plus olanzapine seems to be more effective than monotherapy with a mood stabiliser in preventing manic episodes.

Antidepressive Agents↗
PubMed2005

Rectal fistulas after prostate brachytherapy.

PURPOSE: To compare the rectal and prostatic radiation doses for a prospective series of 503 patients, 44 of whom developed persistent rectal bleeding, and 2 of whom developed rectal-prostatic fistulas. METHODS AND MATERIALS: The 503 patients were randomized and treated by implantation with 125I vs. 103Pd alone (n = 290) or to 103Pd with 20 Gy vs. 44 Gy supplemental external beam radiotherapy (n = 213) and treated at the Puget Sound Veterans Affairs Medical Center (n = 227), Schiffler Cancer Center (n = 242) or University of Washington (n = 34). Patients were treated between September 1998 and October 2001 and had a minimum of 24 months of follow-up. The patient groups were treated concurrently. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urological Association and Radiation Therapy Oncology Group criteria, at 1, 3, 6, 12, 18, and 24 months. Patients who reported Grade 1 or greater Radiation Therapy Oncology Group rectal morbidity were interviewed by telephone to clarify details regarding their rectal bleeding. Those who reported persistent bleeding, lasting for >1 month were included as having Grade 2 toxicity. Three of the patients with rectal bleeding required a colostomy, two of whom developed a fistula. No patient was lost to follow-up. The rectal doses were defined as the rectal volume in cubic centimeters that received >50%, 100%, 200%, or 300% of the prescription dose. The rectum was considered as a solid structure defined by the outer wall, without attempting to differentiate the inner wall or contents. RESULTS: Persistent rectal bleeding occurred in 44 of the 502 patients, 32 of whom (73%) underwent confirmatory endoscopy. In univariate analysis, multiple parameters were associated with late rectal bleeding, including all rectal brachytherapy indexes. In multivariate analysis, however, only the rectal volume that received >100% of the dose was significantly predictive of bleeding. Rectal fistulas occurred in 2 patients (0.4%), both of whom had received moderate rectal radiation doses and extensive intervention for rectal bleeding. CONCLUSION: Partly on the basis of data from others and data presented here, we believe that the incidence of rectal fistulas can be much lower than in our series. High rectal radiation doses should be avoided a priori, to minimize the likelihood of rectal bleeding, and hence the likelihood that invasive procedures will be performed.

Aged↗
PubMed2003

Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: effects of naltrexone.

RATIONALE: A positive relationship exists between chronic ethanol intoxication experiences and the severity of neural hyperactivity and withdrawal seizures. An important possibility is that withdrawal reactions also influence the motivation to obtain and consume ethanol. OBJECTIVES: To test this hypothesis, the effects of ethanol-cues on the recovery of extinguished ethanol-seeking and the reversal of this effect by naltrexone, were determined in non-dependent rats and in rats subjected to single versus repeated ethanol intoxications. METHODS: Rats were trained to self-administer and discriminate between 10% ethanol and water. Instrumental responding then was extinguished and the effects of exposure to ethanol and water cues were determined. Subsequently, rats were divided into three groups and exposed to control vapor (CTRL), to 12-day ethanol vapor prior to withdrawal (SW), or to three cycles of 3-day intoxication experiences (MW), respectively. Following intoxication, reacquisition and breaking point for ethanol self-administration and cues-induced reinstatement of drug-seeking were investigated. RESULTS: Ethanol cues significantly reinstated responding in the pre- and post-dependence test, but no significant differences between groups was observed. However, the ability of naltrexone to attenuate the response-reinstatement was significantly reduced in MW rats. Moreover, in the progressive ratio schedule, the breaking points for ethanol were significantly increased in the MW animals. CONCLUSIONS: The results suggest that repeated intoxication did not enhance cue-induced reinstatement of ethanol-seeking. However, naltrexone effects on cues-induced "relapse" appear to be attenuated in MW rats.

Alcoholic Intoxication↗
PubMed2003

Escalation of cocaine self-administration does not depend on altered cocaine-induced nucleus accumbens dopamine levels.

Previous studies showed that prolonged access to cocaine or heroin self-administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacokinetics and/or efficacy in increasing dopamine (DA) levels in the nucleus accumbens (NAcc) during cocaine intake escalation. In experiment 1, both ShA and LgA rats were challenged with passive intravenous administration of cocaine (0.125-1 mg/injection). Regardless of the doses tested, there was no difference between groups in the ability of cocaine to increase NAcc DA levels and no group differences in the temporal profile of dialysate cocaine levels. In experiment 2, cocaine and DA concentrations were measured during cocaine self-administration. Self-administration produced sustained increases of DA in the NAcc with LgA rats maintaining greater steady levels of DA (750% of baseline) than ShA rats (400% of baseline). The difference in the LgA versus ShA rats was not due to differences in the efficacy of cocaine to elevate DA levels, or in the rate of cocaine metabolism, but was directly related to the amount of self-administered cocaine. These findings show that changes in cocaine efficacy or pharmacokinetics do not play a critical role in cocaine intake escalation.

Animals↗
PubMed2003

Auditory cortex lesions in the rat impair both temporal acuity and noise increment thresholds, revealing a common neural substrate.

Temporal acuity for acoustic transients in rats with bilateral auditory cortex lesions (n = 6) was compared with that of sham-surgery control rats (n = 4), using a standard gap-detection method. A comparison of sensitivity to quiet gaps in noise and dark gaps in light tested for a cross-modal effect of the lesion. The groups were compared also in their sensitivity to noise offset, to noise increments, and to noise pulses presented in quiet. Stimulus detection was assessed with the startle reflex modification procedure, which uses changes in reflex expression caused by stimuli presented immediately before reflex elicitation as the objective evidence for their detection. There were no group differences in sensitivity to noise offset, noise pulses, or dark gaps in light. In contrast, the lesion reduced sensitivity to noise increments and eliminated gap detection. These deficits were maintained for 1 month and only partially recovered 2 months after surgery. The data indicate that the auditory cortex is critically important for temporal acuity in hearing, and suggest that its contribution to gap detection is to enhance the salience of noise increments at the end of the gap.

Acoustic Stimulation↗
PubMed2002

Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze.

Perturbations in serotonin [5-hydroxytryptamine (5-HT)] neurotransmission have been implicated in several psychiatric illnesses including depression and anxiety disorders. It is not yet clear, however, which of the 14 currently identified 5-HT receptor subtypes in the brain participate in the regulation of emotional states. This study investigates a role for the 5-HT(1B) receptor subtype in anxiety-related behaviors using the elevated plus-maze paradigm in rats. The selective 5-HT(1B) receptor agonist 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94,253; 1--5.6 mg/kg) dose-dependently decreased the amount of exploration on the open arms of the plus-maze without altering overall locomotor activity. This 5-HT(1B) agonist-induced increase in anxiety-like behavior was dose-dependently reversed by coadministration of the selective 5-HT(1B/1D) receptor antagonist 2'-methyl-4'-(5-methyl[1,2,4]oxadiazol-3-yl)-biphenyl]-amide (GR 127,935). There was no significant effect of GR 127,935 administration alone on plus-maze behavior. These results indicate that 5-HT(1B) receptor activation increases anxiety-like behavioral responses as measured by the elevated plus-maze. Since 5-HT(1B) receptors modulate the activity of multiple neurotransmitter systems that have been implicated in anxiety disorders, these findings suggest that this receptor subtype may represent an important therapeutic target for the treatment of anxiety.

Animals↗