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Biomedical subjects

H Lublin

Publications and source records attributed to H Lublin.

At least 19 recordsLinked to original sources

Long-term effectiveness of risperidone and olanzapine in resistant or intolerant schizophrenic patients. A mirror study.

OBJECTIVE: To evaluate the long-term effectiveness of the second generation antipsychotics, risperidone and olanzapine on hospitalization, clinical response, and adherence to therapy after switching from conventional antipsychotics or clozapine in a naturalistic setting of schizophrenic patients. METHOD: Data were registered for periods of identical duration before and after switching. RESULTS: Fifty-seven patients were included. Mean study period was 3.1 +/- 0.2 years. Mean number of in-patient days after switching declined by 78% of the level before switching (P=0.0002). There was no significant differences in ratio responders/non-responders between the subgroups. The number of patients with extrapyramidal symptoms (EPS) was significantly reduced after switching. However, intolerable weight gain led to a lack of adherence to therapy in 18% of the olanzapine-treated patients. CONCLUSION: Long-term treatment with the second generation antipsychotics, risperidone and olanzapine significantly improved the clinical outcome. However, weight gain may be a significant reason for discontinuation of treatment and reducing the long-term adherence to therapy.

Adult↗

Patient-rated versus clinician-rated side effects of drug treatment in schizophrenia. Clinical validation of a self-rating version of the UKU Side Effect Rating Scale (UKU-SERS-Pat).

A self-rating version of the UKU Side Effect Rating Scale has been developed. The present study examines the agreement between patients' self-assessment of side effects and the attending clinicians' ratings. The patient sample consisted of 63 patients with schizophrenia under maintenance treatment with risperidone, clozapine or classical antipsychotics. Approximately two thirds of the patients used concomitant medication with e.g. benzodiazepines, SSRIs, anticholinergics. Most inter-correlations between scores for single, corresponding items, subscores of Psychic, Neurological, Autonomic and Other side effects, as well as the Total Score from the patient version of the UKU Side Effect Self Rating Scale (UKU-SERS-Pat) and the clinician version (UKU-SERS-Clin) were found to be statistically significant. Patients reported side effects more frequently and or rated symptoms more severe than the clinicians. The results support the validity of the SERS-Pat and suggest that patient rated side effects may provide important clinical information not detected by clinician rated interviews. Such information can be utilised both in clinical investigations, in development of treatment programs and for individual patients in clinical practice.

Adult↗

Assessment of patient satisfaction with psychiatric care. Development and clinical evaluation of a brief consumer satisfaction rating scale (UKU-ConSat).

Quality management and quality control of health services has become increasingly important. Central to the concept of quality of care is the patient's (the health care consumer's) own view of the care provided and the treatment outcome. UKU (Udvalg for Kliniske Undersøgelser; that is, Committee for Clinical Trials), a working group within the Scandinavian Society for Psychopharmacology (SSP), has designed a brief consumer satisfaction rating scale, the UKU-ConSat. Based on an extensive literature review, a number of principles related to content, assessment, interview techniques, documentation and standardisation steered the design of the rating scale. UKU-ConSat consists of six items related to the structure and process of treatment care, and two items related to outcome and well-being. A manual accompanies the rating scale with guidelines for how to solicit information from the patient and how to rate each item. A first field trial of the rating scale in 135 inpatients at multiple clinical sites in Finland and Sweden showed that it could be applied to several relevant patient categories (psychotic, affective, neurotic, organic and alcohol and substance abuse disorders). According to both patients and staff the rating scale promises to become useful both for research and for improvement of routine psychiatric services.

Adolescent↗

Clozapine versus typical antipsychotics. A retro- and prospective study of extrapyramidal side effects.

Schizophrenic patients in long-term neuroleptic monotherapy with clozapine (n = 100) and perphenazine, flupenthixol or zuclopentixol (controls, n = 100) were evaluated for extrapyramidal side effects (EPS) (blind) as well as other side effects and mental condition (non-blind). In both groups the patients had received neuroleptic treatment for a total of 14 years (median) and the present antipsychotic (clozapine or control drug) for 5 years. Thus the clozapine-treated patients had previously received traditional neuroleptics for 9 years (median). The study was both retrospective (0.3-19 years for clozapine, 0.3-24 years for control drug, by means of chart information) and prospective (1 year, with video-controlled evaluation of EPS). There was a significantly lower prevalence of tardive dyskinesia (TD) in clozapine treated patients than control patients, although prior to this treatment there were more TD patients in the clozapine group (P < 0.05). This lower level of TD in the clozapine group was related to a lower induction of new cases (P < 0.001) and a tendency towards greater disappearance of TD in the clozapine than in the control group (P = 0.07). Clozapine treated patients without TD had started clozapine and ceased traditional neuroleptics at an earlier age than those with TD. Parkinsonian signs were seen in 33% of the clozapine patients versus 61% of the control patients, mainly as hypokinesia; tremor in 3% versus 11% and rigidity in 0 versus 19%. Psychic akathisia was found in 14% versus 40% and motor akathisia in 7% versus 29% of the patients, all differences significantly in favor of clozapine. Clozapine treated patients also had less neuroleptic-induced emotional indifference and depression, but more autonomic side effects than controls.

Adult↗

Extrapyramidal symptoms during long-term treatment with antipsychotics: special focus on clozapine and D1 and D2 dopamine antagonists.

In schizophrenic patients in maintenance treatment, clozapine, compared to classic neuroleptics, induces relatively few extrapyramidal syndromes (EPS), especially less akathisia and tremor and usually no dystonia or rigidity. In patients with dyskinetic movements (acute or tardive) induced by other neuroleptics, clozapine may reduce or even remove dyskinesia or permit it to disappear. It cannot, however, be excluded that clozapine can induce dyskinesia in extremely rare cases, but it seems more likely that this is due to previous treatment with classic neuroleptics. The earlier clozapine is started, the less chance of development of dyskinesia. The low level of EPS with clozapine may be linked to the special receptor-binding profile of this drug: during treatment with therapeutic doses of clozapine, the level of D2 receptor blockade is too low (40% to 50% occupancy by positron emission tomography) to induce EPS, and the D1 receptor blockade (also 40% to 50% occupancy) has a lower EPS potential than D2 blockade. This binding profile may at the same time contribute to the special antipsychotic properties of clozapine. Other receptor affinities may contribute to the beneficial effect of clozapine in EPS and schizophrenia.

Antipsychotic Agents↗

Dopamine receptor agonist- and antagonist-induced behaviors in primates previously treated with dopamine receptor antagonists: the pathogenetic mechanisms of acute oral dyskinesia.

Eight Cebus apella monkeys previously treated with dopamine D1 and D2 receptor antagonists were used to elucidate the pathophysiology of acute oral dyskinesia. Five monkeys had mild oral tardive dyskinesia because of previous antagonist treatment. Interactions between the dopamine (DA) D1 receptor agonist SKF 81297 and the DA D2/D3 receptor agonist quinpirole, DA D1 and D2 receptor antagonists, and the anticholinergic biperiden were investigated. SKF 81297, 0.3 mg/kg, induced acute oral dyskinesia and grooming, which were each inhibited by the DA D1 receptor antagonist NNC 756 in a dose-dependent manner. The DA D2 receptor antagonist raclopride enhanced SKF 81297-induced acute oral dyskinesia and suppressed SKF 81297-induced grooming, each with bell-shaped dose-effect curves. Quinpirole, 0.1 mg/kg, induced a hyperarousal syndrome (i.e., increased arousal, stereotypy, and locomotion). Concomitant treatment with SKF 81297 and quinpirole caused an extreme hyperarousal syndrome but antagonized acute oral dyskinesia and grooming, suggesting a synergistic effect of high-efficacy DA D1 and D2/D3 receptor agonists regarding the induction of the hyperarousal syndrome and the antagonism of acute oral dyskinesia and grooming. Biperiden, 0.25 mg/kg, antagonized both the SKF 81297-induced and raclopride-induced acute oral dyskinesia. The results suggest that oral dyskinesia and grooming are independent but most often simultaneously occurring behaviors. Grooming is induced by DA D1 receptor agonists and antagonized by D1 and D2 antagonists and D2/D3 agonists. Acute oral dyskinesia is induced by D1 agonists and lower doses of D2 antagonists, but antagonized by D1 antagonists, D2/D3 agonists, and anticholinergics. These results suggest varying interactions between dopaminergic receptor subtypes in different types of dopaminergic behaviors.

Animals↗

Long-term treatment with low doses of the D1 antagonist NNC 756 and the D2 antagonist raclopride in monkeys previously exposed to dopamine antagonists.

Eight Cebus apella monkeys previously exposed to D1 and D2 antagonists were treated subcutaneously for 8 weeks with the D1 antagonist NNC 756 (0.01 mg/kg), followed by a wash-out period of 4 weeks and treatment with the D2 antagonist raclopride for 8 weeks (end doses 0.01 mg/kg). NNC 756 induced no dystonia, while marked dystonia was induced by raclopride. Mild tolerance to the dystonia-inducing effect of raclopride slowly developed. Both drugs induced significant sedation and mild bradykinesia. Sedation induced by NNC 756 was stronger than that of raclopride, while no differences were found regarding bradykinesia. The sedative effect of both NNC 756 and raclopride increased over time during chronic treatment. No changes in bradykinesia developed. No significant dyskinesia was induced by NNC 756, while raclopride significantly induced both acute and tardive oral dyskinesia. Furthermore, raclopride-induced acute dyskinesia worsened during chronic treatment. Concomitant treatment with NNC 756 tended to reduce the D1 agonist SKF 81297-induced dyskinesia and grooming, while concomitant treatment with raclopride increased SKF 81297-induced dyskinesia and tended to decrease SKF 81297-induced grooming. Chronic treatment with raclopride induced supersensitivity to both the D2/D3 agonist LY 171555 and SKF 81297, while chronic NNC 756 treatment only induced supersensitivity to SKF 81297. The findings indicate that D1 antagonists may induce less dystonia and oral dyskinesia as compared with D2 antagonists and support the hypothesis of both a permissive and an inhibitory interaction between D1 and D2 receptor systems.

Animals↗

Value of symphysiotomy in obstructed labour management and follow-up of 31 cases.

Experience of 32 cases of symphysiotomy carried out in Mozambique and in Botswana is reviewed. Of all cases only 1 was lost to follow-up. The observation period varied from 7 days to 6 months. Among 31 cases examined at discharge or on return from check-up few complications occurred. Vaginal laceration occurred in 3 cases, haematuria in 1 case and wound infection in 1 case. In 2 cases there was significant postoperative pain causing gait problems, but in no case were there significant problems with pain at discharge or at follow-up. It is concluded that the intervention is seldom complicated by severe sequelae, provided strict adherence to given indications is respected. In rural areas in the third world symphysiotomy is a life-saving and simple surgical intervention, which should be regarded as an adjunct measure in some cases with a moderately contracted pelvic outlet incompatible with normal vaginal delivery.

Botswana↗

Chronic treatment with the D1 receptor antagonist, SCH 23390, and the D2 receptor antagonist, raclopride, in cebus monkeys withdrawn from previous haloperidol treatment. Extrapyramidal syndromes and dopaminergic supersensitivity.

The effects of chronic treatment with dopamine (DA) D1 and D2 receptor antagonists were evaluated in eight cebus apella monkeys with mild oral dyskinesia after previous haloperidol treatment. SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists. Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously. SCH 23390 and raclopride induced dystonic syndromes, catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of SCH 23390, while they showed increased sensibility to the dystonic effect of raclopride. Baseline oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment. SCH 23390 induced supersensitivity to the oral dyskinesia- and grooming-inducing effects of SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of SCH 23390 and the unchanged baseline oral dyskinesia during SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade.

Animals↗

Effect of D1 and D2 agonists in primates withdrawn from long-term treatment with haloperidol: the potential role of dopamine D1 receptors in dyskinesia.

The effects of dopamine (DA) D1 and D2 receptor agonists were evaluated in eight Cebus apella monkeys. The monkeys had previously received haloperidol for 2 years, and five of the monkeys had developed mild oral dyskinesia. SKF 81297 (a full D1 agonist) induced marked oral hyperkinesia, consisting of tongue protrusions and licking or chewing movements, most pronounced in the monkeys with pre-existing oral dyskinesia. SKF 38393 and SKF 75670 (partial D1 agonists) also induced some oral dyskinesia, but to a lesser extent than SKF 81297, and with few licking movements. The partial D1 agonists, but not the full agonist, induced sedation. All of the D1 agonists induced grooming behavior, the full D1 agonist to the greatest extent. In the case of SKF 81297, the grooming was closely associated with the licking behavior. Quinpirole (a selective D2 agonist) and apomorphine (a mixed D1/D2 agonist) induced a hyperactive syndrome (nonoral stereotypy with rapid repetitive movements and increased arousal and locomotor activity). Quinpirole induced no grooming behavior and reduced pre-existing oral movements. The data indicate behavioral differences between D1 and D2 receptors and suggest that D1 receptors may be involved in the pathophysiology of some forms of dyskinesia syndromes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.

Adult↗

The effects of dopamine D1 and D2 receptor agonists and antagonists in monkeys withdrawn from long-term neuroleptic treatment.

The effects of dopamine D1 and D2 receptor agonists and antagonists were studied in eight Cebus apella monkeys previously treated with haloperidol for two years. SKF 81297 (specific D1 receptor agonist) induced oral hyperkinesia of variable intensity (P less than 0.01): some of the monkeys developed extreme lip smacking, tonque protrusions and licking movements while others developed only slight lip movements. A combined treatment of SKF 81297 with LY 171555 (full D2 receptor agonist) or SCH 23390 (D1 receptor antagonist) inhibited the oral hyperkinesia induced by SKF 81297 (P less than 0.01, P less than 0.02, respectively). Raclopride (D2 receptor antagonist) did not statistically change oral hyperkinesia (P less than 0.2), although five monkeys showed increased oral movements; most of these monkeys had pre-existing hyperkinesia. Treatment with SCH 23390 or raclopride resulted in an identical dystonic/cataleptic syndrome. SKF 81297 inhibited the dystonia induced by SCH 23390, while it did not significantly affect raclopride dystonia. The investigation indicates that oral dyskinesia may be related to an imbalance in D1 receptor and D2 receptor stimulation in favor of D1 receptors. The question now is whether D1 receptor antagonists, which may have antipsychotic potential, will produce tardive dyskinesia after long-term use.

Animals↗

Behavioural effects of dopamine D-1 and D-2 receptor agonists in monkeys previously treated with haloperidol.

The effects of dopamine D-1 and D-2 receptor agonists were evaluated in five Cebus apella monkeys. During a previous haloperidol treatment (2 years), three of the monkeys had developed oral tardive dyskinesia (tongue protrusion and/or chewing). The partial D-1 agonist, SKF 38393, induced/aggravated oral dyskinesia and slight sedation, but no non-oral repetitive movements. Conversely, the selective D-2 agonist, LY 171555, produced non-oral repetitive movements and increased reactivity (arousal), but no significant change in the oral movements. Apomorphine (a mixed D-1/D-2 agonist) induced non-oral repetitive movements, increased reactivity, and increased oral dyskinesia. Pretreatment with SKF 38393 inhibited the LY 171555-induced non-oral repetitive movements, while in four monkeys the SKF 38393-induced oral movements were inhibited by LY 171555. The results suggest that oral dyskinesia (tardive dyskinesia) is more related to D-1 receptor stimulation than to D-2 receptor supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Antacids in the treatment of duodenal ulcer.

Fifty patients with endoscopically proven pyloric-prepyloric ulcers (PU/PPU) and 50 with duodenal ulcers (DU) completed a six-week double-blind clinical trial initially comprising 124 patients. The antacid-treated patients received 10 ml of an antacid suspension seven times a day (buffering 367.5 mmol acid). Healing rate after three weeks of treatment was 74% in the antacid and 42% in the placebo group (p less than 0.01). After six weeks the corresponding figures were 96 and 68% (p less than 0.001). Regarding the PU/PPU and DU subgroups we found significant differences compared to placebo in the PU/PPU group only. Antacids caused a significantly faster and more perceptible pain relief than placebo. We found no significant correlation between ulcer healing and smoking habits. Regression analyses showed that, besides antacids, ulcer size and peak acid output influenced the healing rate significantly.

Adult↗