Diagnostic performance of chromoendoscopy and narrow band imaging for colonic neoplasms: a meta-analysis.

AIM: We conducted a meta-analysis to compare the diagnostic test performance of chromoendoscopy and narrow band imaging (NBI) for colonic neoplasms. METHOD: MEDLINE, EMBASE and the Cochrane Library were searched (1966 to March 2009). Articles were included if: (i) chromoendoscopy or NBI was used, (ii) sensitivity and specificity were reported; (iii) absolute numbers of true-positive, false-positive, true-negative and false-negative results were provided or could be calculated; and (iv) pathology was used as the reference standard. Sensitivity and specificity were pooled using random effects model. Secondary analyses were conducted by limiting the studies in which magnifying endoscopy was used alone as a diagnostic modality, and polyp size and macroscopic appearance of lesions were not considered. RESULTS: Of 1342 screened articles, 27 met the inclusion criteria. Pooled sensitivity for chromoendoscopy and NBI was 0.94 (95% CI, 0.92-0.95) and 0.94 (0.91-0.97), and specificity was 0.82 (0.77-0.88) and 0.86 (0.83-0.89), respectively. There were no differences in sensitivity (P = 0.99) or specificity (P = 0.54) between the two methods. In the secondary analysis, pooled sensitivity for choromoendoscopy and NBI was 0.93 (95% CI, 0.90-0.97) and 0.96 (0.93-0.99) and specificity was 0.80 (0.73-0.87) and 0.85 (0.78-0.92). respectively. Overall, the pooled false-negative rate was 0.057 (95% CI, 0.040-0.73) for chromoendoscopy and 0.057 (95% CI, 0.028-0.085) for NBI. CONCLUSION: Chromoendoscopy and NBI had similar diagnostic test characteristics in the assessment of colonic neoplasms; however, the false-negative rate for both methods of 5.7% is an unacceptably high rate and currently therefore, neither method is ready for general use.

cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily.

Interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long.

The impact of oral phenylpropanolamine on blood pressure: a meta-analysis and review of the literature.

Oral phenylpropanolamine is commonly used to treat congestion and obesity. Clinicians often wonder what effect it has on blood pressure and whether they are safe in hypertensive patients. The purpose of our systematic review was to assess whether these drugs cause clinically meaningful elevations in pulse or blood pressure. English-language, randomized, placebo-controlled trials of oral phenylpropanolamine in adults with extractable data on pulse or blood pressure were studied. MEDLINE (1966-2003), Embase, the Cochrane library and reviewed article references were used as sources. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate data were extracted. Additional extracted data included demographics, year, study design, study duration, drug dose and frequency, duration of washout and country. Study quality was assessed using the methods of Jadad and data were synthesized using a random effects model using weighted mean differences. In all, 33 trials reporting 48 treatment arms with 2165 patients were included. Phenylpropanolamine increased SBP 5.5 mmHg (95% CI: 3.1-8.0) and DBP 4.1 mmHg (95% CI: 2.2-6.0) with no effect on pulse. Patients with controlled hypertension were not at greater risk of blood pressure elevation. Immediate release preparations had greater effects on blood pressure than sustained release ones. Higher doses and shorter duration use also caused greater increases. Eighteen studies contained at least one treated subjects having blood pressure elevations > or =140/90 mmHg, an increase in SBP > or =15 mmHg or an increase in DBP > or =10 mmHg. In conclusion, phenylpropanolamine caused a small, but significant increase in systolic blood pressure. The effect was more pronounced with shorter-term administration, higher doses of medication and immediate release formulations.

Difficult patient encounters in the ambulatory clinic: clinical predictors and outcomes.

BACKGROUND: One sixth of patient encounters are perceived as difficult by clinicians. Our goal was to assess clinical predictors and outcomes from such encounters. METHODS: Five hundred adults presenting to a primary care walk-in clinic with a physical symptom completed surveys before the visit, immediately after the visit, at 2 weeks, and at 3 months. Patient measurements included mental disorders (PRIME-MD), functional status (Medical Outcomes Study Short-Form Health Survey [SF-6]), satisfaction (RAND 9-item survey), symptom resolution, visit costs, previsit and residual expectations of care, and health services utilization. Measurements from the 38 participating clinicians included the Physician's Belief Scale and physician perception of encounter difficulty (Difficult Doctor-Patient Relationship Questionnaire). RESULTS: Seventy-four patient encounters (15%) were rated as difficult. Patients in such encounters were more likely to have a mental disorder (odds ratio, 2.4; 95% confidence interval, 1.3-4.4), more than 5 somatic symptoms (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), and more severe symptoms (odds ratio, 1.6; 95% confidence interval, 1.04-2.3). Difficult-encounter patients had poorer functional status, more unmet expectations (P=.005), less satisfaction with care (P=.03), and higher use of health services (P<.001). Clinicians with poorer psychosocial attitudes as reflected by higher scores on the Physician's Belief Scale experienced more encounters as being difficult (23% vs 8%; P<.001). CONCLUSIONS: Patients presenting with physical symptoms who are perceived as difficult are more likely to have a depressive or anxiety disorder, poorer functional status, unmet expectations, reduced satisfaction, and greater use of health care services. Physicians with poorer psychosocial attitudes are more likely to experience encounters as difficult.

A meta-analysis of zinc salts lozenges and the common cold.

BACKGROUND: In the United States, the common cold has been estimated to cost more than $3.5 billion a year. Despite several randomized clinical trials, the effect of treating colds with zinc salts lozenges remains uncertain because of conflicting results. OBJECTIVE: To conduct a meta-analysis of published randomized clinical trials on the use of zinc salts lozenges in colds using a random effects model. RESULTS: Eight clinical trials of treating adults with zinc salts lozenges were identified. After excluding 2 studies that used nasal inoculation of rhinovirus, 6 trials were combined and analyzed. The summary odds ratio for the presence of any cold symptoms at 7 days was 0.50 (95% confidence interval, 0.19-1.29). CONCLUSION: Despite numerous randomized trials, the evidence for effectiveness of zinc salts lozenges in reducing the duration of common colds is still lacking.

Adult Kawasaki disease. Report of two cases treated with intravenous gamma globulin.

There are 36 reports in the English-language literature of Kawasaki disease in adults. We present two additional cases, in one of which retinal vasculitis developed, a previously unreported complication antemortem. We report the first use of intravenous gamma globulin in the United States for treatment of adult-onset Kawasaki disease and review the pertinent literature.

The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta-analysis.

BACKGROUND: Herpes zoster is a common affliction in older patients, with up to 15% experiencing some residual pain in the distribution of the rash several months after healing. Despite numerous randomized clinical trials, the effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia remains uncertain because of conflicting results. METHODS: Meta-analysis of published randomized clinical trials on the use of acyclovir to prevent postherpetic neuralgia using the fixed-effects model of Peto. RESULTS: Thirty clinical trials of treatment with oral acyclovir in immunocompetent adults were identified. After excluding studies with duplicate data, suboptimal and topical dosing, non-placebo-controlled or nonrandomized designs, and those using intravenous acyclovir, 5 trials were found to be homogeneous and were combined for analysis. From these trials, the summary odds ratio for the incidence of "any pain" in the distribution of rash at 6 months in adults treated with acyclovir was 0.54 (95% confidence interval, 0.36-0.81). CONCLUSION: Treatment of herpes zoster with 800 mg/d of oral acyclovir within 72 hours of rash onset may reduce the incidence of residual pain at 6 months by 46% in immunocompetent adults.

Cyclobenzaprine and back pain: a meta-analysis.

BACKGROUND: Back pain is a common problem for which cyclobenzaprine hydrochloride is frequently prescribed. OBJECTIVE: To perform a systematic review of cyclobenzaprine's effectiveness in the treatment of back pain. METHODS: We searched MEDLINE, PsycLIT, CINAHL, EMBASE, AIDSLINE, HEALTHSTAR, CANCERLIT, the Cochrane Library, Micromedex, Federal Research in Progress, and the references of reviewed articles, and contacted Merck, Sharpe and Dohme for English-language, randomized, placebo-controlled trials of cyclobenzaprine in adults with back pain. Outcomes included global improvement and 5 specific domains of back pain (local pain, muscle spasm, range of motion, tenderness to palpation, and activities of daily living). Study quality was assessed using the methods of Jadad. Summary outcomes were obtained using a random-effects model. RESULTS: Patients treated with cyclobenzaprine were nearly 5 times (odds ratio, 4.7; 95% confidence interval, 2.7-8.1) as likely to report symptom improvement by day 14 as were those treated with placebo. Slightly fewer than 3 individuals (2.7; 95% confidence interval, 2.0-4.2) needed treatment for 1 to improve. The magnitude of this improvement was modest, with an effect size of 0.38 to 0.58 in all 5 outcomes (local pain, muscle spasm, tenderness to palpation, range of motion, and activities of daily living). Treatment efficacy for these 5 outcomes was greatest early, in the first few days of treatment, declining after the first week. Patients receiving cyclobenzaprine also experienced more adverse effects, the most common being drowsiness. CONCLUSIONS: Cyclobenzaprine is more effective than placebo in the management of back pain; the effect is modest and comes at the price of greater adverse effects. The effect is greatest in the first 4 days of treatment, suggesting that shorter courses may be better. Studies comparing the relative value of acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclobenzaprine individually and in combination in the treatment of back pain are needed.

The value of screening for psychiatric disorders in rheumatology referrals.

BACKGROUND: Musculoskeletal complaints are common and often unexplained and often lead to rheumatology referrals. The prevalence of psychiatric disease in patients with musculoskeletal complaints is unknown. OBJECTIVES: To determine the prevalence of common psychiatric disorders among patients referred to a rheumatology clinic and the likelihood of establishing a rheumatic diagnosis if a psychiatric disorder is present. DESIGN: Prospective diagnostic survey. SETTING: Two hospital-based rheumatology clinics and a general medicine clinic. PARTICIPANTS: A consecutive sample of newly referred patients (n = 185) and their rheumatologists (n = 9). INTERVENTION: Before their visit, all patients filled out a self-administered version of PRIME-MD (Primary Care Evaluation of Mental Disorders), a questionnaire that makes Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: Primary Care Version, diagnoses of depressive, anxiety, and somatoform disorders. After the visit, the study rheumatologists, who were unaware of the PRIME-MD results, completed a questionnaire regarding their diagnostic assessment. These patients were compared with 210 patients with musculoskeletal complaints who were cared for in a general medicine clinic. MAIN OUTCOME MEASURES: Psychiatric and rheumatic disorders. RESULTS: Compared with patients with musculoskeletal complaints in a general medicine clinic, patients referred to a rheumatology clinic had a higher prevalence of psychiatric disease (40% vs 29%; P = .008), had an almost 2-fold higher prevalence of anxiety disorders, and were more likely to have multiple psychiatric disorders (odds ratio = 2.70, 95% confidence interval = 1.50-5.00). The likelihood of a psychiatric disorder differed among patients with connective tissue disease, nonsystemic articular or periarticular disorders, and nonarticular disorders (27%, 38%, 55%, respectively; P = .006). In a best-fitting logistic regression model, psychiatric disorders markedly decreased the likelihood of a connective tissue disease (odds ratio = 0.24, 95% confidence interval = 0.09-0.62). CONCLUSIONS: Forty percent of patients referred to a rheumatology clinic in this study had a psychiatric disorder, and its presence predicted a lower likelihood of a connective tissue disease. Prospective studies are needed to determine if screening for psychiatric disease before referring patients with unexplained musculoskeletal complaints would reduce costs or improve recognition of potentially treatable psychiatric disorders.

Clinical predictors of mental disorders among medical outpatients.

BACKGROUND: Mental disorders are common among primary care patients and often not detected by primary care physicians. We report on clinical cues that may allow physicians to target patients for psychiatric screening. METHODS: Two hundred fifty consecutive adults presenting to a walk-in clinic completed previsit surveys assessing demographics, symptom characteristics, recent stress, functional status (Medical Outcomes Study Short Form-6), and mental disorders (Primary Care Evaluation of Mental Disorders [PRIME-MD]). Patients with positive findings for a mental disorder on the PRIME-MD underwent a semistructured interview. Immediately after the visit, physicians completed the Difficult Doctor Patient Relationship Questionnaire. RESULTS: Patients averaged 50.5 years of age (range, 18-92 years). Little more than half were women (53%); 43%, white; 44%, African American; 8%, Hispanic; and 6%, other. Twenty-six percent had an underlying mental disorder; 11% had more than 1 mental disorder. Sixteen percent had a depressive disorder; 6%, major depression; 11%, an anxiety disorder; 2%, panic disorder; and 9%, a somatoform disorder. Independent correlates of a mental disorder included reporting recent stress (odds ratio [OR], 6.7; 95% confidence interval [CI], 3.3-13.6), having 5 or more physical symptoms (OR, 4.0; 95% CI, 2.1-7.9), or reporting health to be less than very good (OR, 2.2; 95% CI, 1.1-4.3). There was a stepwise increase in the likelihood of having a mental disorder and number of correlates present. Among patients with no predictors, only 2% had an underlying mental disorder, compared with 72% among patients with all 3 clinical predictors. CONCLUSIONS: Patients who report recent stress, 5 or more physical symptoms, or poor health are more likely to have an underlying mental disorder. These clinical cues may allow clinicians to select patients in whom formal screening for mental disorders would be particularly fruitful.

Platelet serotonin markers and depressive symptomatology.

Dysfunction of brain serotonergic symptoms may be a factor in the mood and behavioral disturbances associated with depression. Platelet serotonin measures represent indirect but easily obtainable indices of brain serotonin function. To examine the specificity of relationships between cognitive and vegetative symptom groupings and platelet serotonin measures, we assessed 35 depressed outpatients using the Hamilton Rating Scale for Depression and collected platelets after a minimum 3-week drug-free period. Platelets were also collected from 14 controls. The results showed that depressed patients had lower platelet serotonin (5-HT) uptake site density values than controls and that 5-HT uptake site density values were inversely correlated with the severity of cognitive symptoms of depression. Platelet 5-HT2 receptor density values were higher in depressed patients than controls, and there was a trend toward a direct correlation between the cognitive symptoms of depression and 5-HT2 receptor density values. Neither platelet measure showed any relationship with the severity of the vegetative symptoms of depression.

Depressive and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome.

PURPOSE: To identify the predictors of depressive and anxiety disorders in general medical patients presenting with physical complaints and to determine the effect of these mental disorders on patient outcome. PATIENTS AND METHODS: In this cohort study, 500 adults presenting to a general medicine clinic with a chief complaint of a physical symptom were interviewed with PRIME-MD to diagnose DSM-IV depressive and anxiety disorders. Clinical predictors were identified by logistic regression analysis. Outcomes were assessed immediately postvisit and at 2 weeks and 3 months. These included symptomatic improvement, functional status, unmet expectations, satisfaction with care, clinician-perceived patient difficulty, and health care utilization and costs. RESULTS: A depressive or anxiety disorder was present in 146 (29%) of the patients. Independent predictors of a mental disorder included recent stress, multiple physical symptoms (ie, 6 or more), higher patient ratings of symptom severity, lower patient ratings of their overall health, physician perception of the encounter as difficult, and patient age less than 50. Patients with depressive or anxiety disorders were more likely to have unmet expectations postvisit (20% versus 8%, P < 0.001), be considered difficult (26% versus 11%, P < 0.0001), and report persistent psychiatric symptoms and ongoing stress even 3 months following the initial visit. Psychiatric status was not associated with symptomatic improvement, health care utilization, or costs. CONCLUSION: Simple clinical clues in patients with physical complaints identify a subgroup who may warrant further evaluation for a depressive or anxiety disorder. Such disorders are associated with unmet patient expectations and increased provider frustration.

Treatment of chronic headache with antidepressants: a meta-analysis.

BACKGROUND: Although antidepressants are often used for preventing chronic headache, their effectiveness is uncertain. METHODS: We performed a meta-analysis of English-language, randomized placebo-controlled trials of antidepressants as prophylaxis for chronic headache. RESULTS: Thirty-eight trials were included. Because some compared more than one drug with placebo, 44 study arms were combined using a random effects model. Twenty-five studies focused on migraines, 12 on tension headaches, and 1 on both. Nineteen used tricyclic antidepressants, 18 serotonin antagonists, and 7 selective serotonin reuptake inhibitors. Patients receiving antidepressants were twice as likely to report headache improvement (rate ratio [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.4). Because 31% (95% CI: 23% to 40%) more treated patients improved than those receiving placebo, clinicians would need to treat 3.2 patients for 1 patient to improve. The average amount of improvement (standardized mean difference) was 0.94 (95% CI: 0.65 to 1.2), an effect considered large. Treated patients also consumed less analgesic medication (standardized mean difference, -0.7; 95% CI: -0.5 to -0.94). There were no differences in outcomes among the three classes of agents studied or by the type of headache (migraine vs. tension), quality score, length of treatment, or percentage of patients lost to follow-up. Assessment of depression across studies was insufficient to determine if the effects were independent of depression. CONCLUSION: Antidepressants are effective in preventing chronic headaches. Whether this is independent of depression and whether there are differences in efficacy by class of agent needs further study.

Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis.

BACKGROUND: Functional gastrointestinal disorders are common, accounting for up to 50% of gastroenterology referrals, and several randomized controlled trials have evaluated antidepressant therapy for their treatment. METHODS: We performed a meta-analysis of published, English-language, randomized clinical trials on the use of antidepressants for the treatment of patients with functional gastrointestinal disorders. RESULTS: Twelve randomized placebo-controlled trials of antidepressant treatment of functional gastrointestinal disorders were identified. One was excluded for using a combination of a tricyclic and neuroleptic agent. The medications included tricyclic antidepressants (amitriptyline [n = 3], clomipramine [n = 1], desipramine [n = 2], doxepin [n = 1], and trimipramine [n = 2]), and the antiserotonin agent, mianserin (n = 2). In addition, one trial compared two different antidepressants (mianserin and clomipramine) with placebo. Data were abstracted for the dichotomous outcome of symptom improvement in seven studies, and for the continuous variable of pain score in eight studies. The summary odds ratio for improvement with antidepressant therapy was 4.2 (95% confidence interval [CI]: 2.3 to 7.9), and the average standardized mean improvement in pain was equal to 0.9 SD units (95% CI: 0.6 to 1.2 SD units). On average 3.2 patients needed to be treated (95% CI: 2.1 to 6.5 patients) to improve 1 patient's symptom. CONCLUSION: Treatment of functional gastrointestinal disorders with antidepressants appears to be effective. Whether this improvement is independent of an effect of treatment on depression needs further evaluation.

Antihypertensive ureidopiperidines.

The synthesis of a series of 1-aralkyl-4-ureidopiperidines is reported. These compounds are related to the benzamidopiperidines exemplified by indoramin. Some of the ureidopiperidines are more potent antihypertensive agents than their benzamidopiperidine counterparts. Two examples, 1-(2-thenoyl)-3-[1-[2-(3-indolyl)ethyl]piperid-4-yl]urea and 1-(2-thenoyl)-3-[1-[4-(4-fluorophenyl)-4-oxobutyl]piperid-4-yl]urea (19 and 58), emerged as the most potent antihypertensive agents in this series.

Chronic stress enhances ibotenic acid-induced damage selectively within the hippocampal CA3 region of male, but not female rats.

The purpose of this investigation was to assess the ability of the hippocampus to withstand a metabolic challenge following chronic stress. An N-methyl-d-aspartate receptor excitotoxin (ibotenic acid, IBO) was infused into the CA3 region of the hippocampus following a period of restraint for 6 h/day/21 days. Following the end of restraint when CA3 dendritic retraction persists (3 to 4 days), rats were infused with IBO (or vehicle) into the CA3 region of the hippocampus. Stressed male rats showed significantly more CA3 damage after IBO infusion relative to controls and the saline-infused side. Moreover, IBO-exacerbation of damage in males was not observed in the CA3 region 3 to 4 days after acute stress (6 h restraint), nor in the CA1 region after chronic stress. Females were also examined and chronic stress did not exacerbate IBO damage in the CA3 region. Overall, these results demonstrate that chronic stress compromises the ability of the hippocampus to withstand a metabolic challenge days after the chronic stress regimen has subsided in male rats. Whether the conditions surrounding CA3 dendritic retraction in females represents vulnerability is less clear and warrants further investigation.

Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations.

The predictive ability of electron-beam computed tomography (EBCT) for coronary heart disease outcomes, particularly hard coronary outcomes (myocardial infarction or death), has been questioned in asymptomatic populations. Our objective was to synthesize data on the use of EBCT for determining cardiovascular prognosis in asymptomatic populations. Studies were identified using standard systematic review methods. The outcome of interest was relative risk for myocardial infarction or sudden death, and combined events including revascularization. Nine articles met the inclusion criteria, of which 5 were of independent studies. Using meta-analytic techniques to synthesize prognostic data, there was an increased risk (summary risk ratio 8.7, 95% confidence interval 2.7 to 28.1) of a combined outcome of nonfatal myocardial infarction or death or revascularization if the calcium score was above a median score. Similarly, there was an increased risk for hard events: myocardial infarction or death (summary risk ratio 4.2, 95% confidence interval 1.6 to 11.3). However, there was significant heterogeneity in the studies' quality and patient populations. Although EBCT appears to predict combined and hard coronary outcomes similarly in high risk, asymptomatic populations, these results should be interpreted with caution. Further study is needed on the incremental value of EBCT over conventional risk prediction before this test is used in screening asymptomatic populations.

The effects of kainic acid lesions on locomotor responses to haloperidol and clozapine.

Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneous and amphetamine-elicited locomotion. The present study determined if KA lesions alter the suppressive effects of the antipsychotic drugs, haloperidol and clozapine, on spontaneous and amphetamine-elicited locomotor behavior. Young adult male rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex, and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to drug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg s.c.) were greater in lesioned animals than controls. In addition, the level of spontaneous activity and/or amphetamine-elicited hyperlocomotion observed in lesioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg s.c.) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar in lesioned and control rats, although lesioned rats were more active than controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol, yet uniquely sensitive to suppression by clozapine.

The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine.

The antipsychotic drugs haloperidol and clozapine have the common action of increasing dopamine metabolism in the striatum (nucleus accumbens, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain regions which project directly or indirectly to the striatum. In the present study, dopamine metabolism in subregions of the striatum was examined in rats with KA lesions after acute and chronic haloperidol or clozapine administration. The main findings was that the elevating effect of acute haloperidol treatment on the dopamine metabolite, DOPAC, was blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition, the elevating effects of both acute and chronic haloperidol treatment on dopamine turnover were attenuated in the laterodorsal caudate-putamen of KA-lesioned rats. The levels of dopamine, DOPAC, and HVA after chronic clozapine treatment were greater in KA-lesioned than control rats. These results indicate that dopaminergic responses to haloperidol may be diminished by limbic-cortical neuropathology, while such pathology does not significantly alter dopaminergic responses to clozapine.

Testing the effects of hypnotics on memory via the telephone: fact or fiction?

The two benzodiazapines used in this experiment, namely midazolam and flunitrazepam, have both been shown to have effects on memory processing in laboratory studies. In spite of the potential hazards involved in real life testing, it should be possible to replicate such findings in everyday environments and it is argued that a successful replication would be a very meaningful extension to the existing laboratory data. The present study was successful in producing significant "hangover" effects in healthy volunteers using a novel "user-friendly" telephone testing technique. Compared to placebo, the two hypnotics reduced speed of processing in tasks which required retrieval from long-term semantic memory (semantic verification) and the manipulation of material in working memory (syntactic reasoning). We suggest that this new method offers the potential for carrying out large-scale psychopharmacological studies with real patients and achieves a meaningful step forward in the search for ecological validity.