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Biomedical subjects

J Gerlach

Publications and source records attributed to J Gerlach.

At least 73 records · Page 4Linked to original sources
PubMed1994

Oral versus depot administration of neuroleptics in relapse prevention.

Depot administration of neuroleptic drugs offers several advantages in the long-term maintenance therapy of chronic schizophrenic patients. The major advantage is the assurance of compliance leading to fewer relapses and rehospitalizations. Depot neuroleptics also eliminate bioavailability problems related to absorption and first pass metabolism and give a stable plasma concentration. Finally, depot neuroleptics assure better and safer possibilities to use the lowest effective dose principle, thereby reducing the frequency of side effects, including the subjectively distressing mental side effects such as akathisia, dysphoria and neuroleptic-induced deficit syndrome. Disadvantages include delayed disappearance of side effects after discontinuation and, for many patients, a feeling of being controlled. Administered in the proper way, with suitable information to the patient and relatives, depot neuroleptics improve the quality of the antipsychotic treatment, reduce relapse frequency, stabilize the therapeutic effect and diminish the level of side effects.

Administration, Oral↗
PubMed1994

Amino acid metabolism by hepatocytes in a hybrid liver support bioreactor.

The amino acid patterns of medium perfusate in a liver cell bioreactor developed for a hybrid liver support system have been measured. There were considerable changes in the concentrations of glutamic acid, glutamine, alanine, arginine, ornithine and branched chain amino acids during the first 10 days which is indicative of dynamic cellular metabolism. From day 15, steady state conditions of nitrogen metabolism are reflected by stable amino acid turnover. Monitoring of urea, K+, and P-450 activity suggests that hepatocytes have switched to a stable protein synthesis with a general amino acid uptake and keto acid release following cell volume increase.

Amino Acids↗
PubMed1994

Hybrid liver support system in a short term application on hepatectomized pigs.

A short term application of a hybrid liver support system in circuits with continuous plasma-separation was investigated in a model of hepatectomized pigs under general anesthesia. Primary pig hepatocytes were immobilized in a bioreactor with three independent capillary systems. An immune barrier is achieved by avoiding the direct contact of blood cells with the hepatocytes by a plasmaseparation step and by an outflow filtration within the reactor. In three groups (hepatectomized pigs and system with- or without hepatocytes as well as untreated pigs with system without hepatocytes), the short term metabolism of the reactors was positively demonstrated by investigating ammonia detoxification, phenylalanine- and lactate metabolism. Limitations of the presented model are discussed.

Ammonia↗
PubMed1994

Alpha-keto acid metabolism by hepatocytes cultured in a hybrid liver support bioreactor.

Isolated pig liver cells cultured using a perfusion technique were analyzed over 39 days to test their ability to change the perfusate alpha-keto acid profile. While the pyruvate concentration in the culture medium decreased as of the first day, the alpha-ketoglutarate (KG), alpha-ketoisocaproate (KIC), alpha-ketoisovalerate (KIV) and alpha-keto-beta-methyl-n-valerate (KMV) were synthesized immediately and released by the liver cells. The metabolic capacity of the cell culture system increased up to day 10, decreased during the following 5 days and reached a steady state beyond day 15, which was maintained for at least 30 days. The branched chain alpha-keto acid release, in particular alpha-ketoisocaproate, reflects an effective transamination capacity of the newly developed culture system and shows an intact protein biosynthesis for at least 30 days in vitro.

Animals↗
PubMed1994

Motor and mental side effects of clozapine.

Long-term experience with clozapine has shown that the agent has a motor and mental side effect profile that is distinct in many ways from classical neuroleptics. It can produce a parkinsonian-like bradykinesia and mild akathisia, but no rigidity and rarely tremor. In patients with tardive dyskinesia induced by other neuroleptics, clozapine permits the dyskinesia to disappear in about half the cases. That clozapine may induce tardive dyskinesia in extremely rare cases cannot be excluded, but it seems more likely that this tardive dyskinesia in clozapine-treated patients is due to previous treatment with classical neuroleptics. The earlier clozapine is started, the less chance for development of tardive dyskinesia. As do other neuroleptics, clozapine can elicit sedation and asthenia, but corresponding to the motoric extrapyramidal syndrome, clozapine causes emotional indifference ("mental parkinsonism"), depression, and restlessness to a significantly lesser degree, which may be of importance in the higher compliance seen with this drug.

Affective Symptoms↗
PubMed1994

[Cell culture model for hepatocyte culture in bioreactors for metabolic utilization in hybrid liver support system].

Hybrid systems with hepatocyte cultures in bioreactors are in development for therapeutical liver assistance. Here, a culture model with a special bioreactor construction was developed: Capillary membrane systems create a three dimensional artificial framework for hepatocyte adhesion, aggregation and reorganization of tissue structures. Many of small parallel capillary membrane units perfuse a few hepatocytes. Different capillary materials enable different functions. Cell perfusion between independent plasma inflow and outflow capillaries, independent oxygen supply and carbon dioxide removal as well as a co- culture with sinusoidal endothelial cells are possible. An in vitro study with bioreactors (n = 9), containing 2.5 x 10(9) pig hepatocytes was performed, measuring external metabolism of the cells: cytochrome P450-activity (midazolam metabolism, lidocaine/MEGX-test), synthesis (albumin), liver function test (galactose elimination) and cell alteration (LDH, GOT, GLDH, GPT, gamma GT) were investigated. The results demonstrate that external function of primary hepatocytes can be maintained over a period of at least three weeks.

Animals↗
PubMed1994

Clozapine treatment in Denmark: concomitant psychotropic medication and hematologic monitoring in a system with liberal usage practices.

BACKGROUND: Clozapine has been utilized in Denmark since the early 1970s. This study examines doses, concomitant psychotropics, and leukocyte counts. METHOD: All psychiatric hospitals in Denmark were asked for copies of all their clozapine monitoring forms, which were then personally reviewed by the authors. RESULTS: Forms from 656 patients were collected from 32 hospitals. The male/female ratio was 2/1; the median age, 38 years (range, 18-80). Thirty-five percent received concomitant antipsychotics, 28% benzodiazepines, 19% anticholinergics, 11% antidepressants, 8% antiepileptics, (carbamazepine, valproate, and phenobarbital), and 2% lithium. While there were no gender differences with respect to concurrent psychotropics, women received lower doses of clozapine than men (median dose, women 300 mg/day and men 400 mg/day, p < .02). Ten percent had had a neutrophil count < 2000/microL (3.2% < 1500/microL). Five percent had repeated neutrophil counts < 2000/microL (1.5% < 1500/microL). There were two cases of agranulocytosis; both patients fully recovered upon withdrawal of clozapine. Clozapine was discontinued because of hematologic abnormalities in only five other cases (0.8%). CONCLUSION: While use of concomitant psychotropics during clozapine treatment should be limited because of an increased risk of complications, a totally restrictive policy might deprive certain patients of the benefits of clozapine treatment. There appears to be a benign form of granulocytopenia that does not always necessitate discontinuation, provided there is close follow-up.

Adolescent↗
PubMed1993

Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol.

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.

Administration, Oral↗
PubMed1993

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↗
PubMed1993

Comparison of pig hepatocyte isolation using intraoperative perfusion without warm ischemia and isolation of cells from abattoir organs after warm ischemia.

Enzymatic hepatocyte isolation using warm ischemic pig livers from an abattoir was compared with isolation using in situ perfused organs. Using organs from animals of 30 kg body mass (BM), the intraoperative perfusion showed superior results. The use of livers from abattoir pigs of 40-50 kg BM after warm ischemia resulted in a lower yield of hepatocytes and in high rates of injured cells. The mean yield in the intraoperative perfusion group was 68 +/- 11% (wet weight), the maximum yield in the abattoir organ group was 58%. The mean viability in the intraoperative perfusion group was 65 +/- 14% (trypan blue) compared with a maximum viability of 39% in the abattoir liver group. Additional purification by density gradient centrifugation improved the viability of the abattoir liver group to a mean of 95% (trypan blue). The use of pig livers from large abattoir animals required additional purification steps to improve viability since the cell yield is considerably lower than with intraoperative organ perfusion. In general, hepatocyte isolation from abattoir organs is not recommended.

Abattoirs↗
PubMed1993

The St. Hans Rating Scale for extrapyramidal syndromes: reliability and validity.

The St. Hans Rating Scale (SHRS) is a multidimensional rating scale for the evaluation of neuroleptic-induced hyperkinesia, parkinsonism, akathisia and dystonia. This scale and the Abnormal Involuntary Movement Scale (AIMS) were tested by 7 raters (2 experienced, 2 less experienced and 3 totally inexperienced) in 30 psychiatric patients with tardive dyskinesia (TD). The test was performed 3 times in the same patients: 1) live evaluation during a video recording, 2) evaluation 2 weeks later from the videotape, and 3) evaluation after another 2 weeks from the same videotape. The intrarater reliability was high in the experienced group (0.91-0.96 for SHRS hyperkinesia scale, 0.80-0.84 for AIMS, and 0.82-0.97 for SHRS total parkinsonism). No significant changes occurred from live to video evaluation. The interrater reliability coefficient for the experienced group was also high: 0.89-0.95 for the SHRS hyperkinesia scale, 0.76-0.85 for the AIMS scale and 0.95-0.98 for the SHRS parkinsonism scale. The less experienced and the inexperienced raters had coefficients for intra- and interrater reliability that were 0.10 and 0.20 lower, respectively. The SHRS parkinsonism scale had a high construct validity, as determined by the homogeneity coefficients of Cronbach (0.82) and Loevinger (0.43). The corresponding coefficients for the hyperkinesia scales were low, in agreement with the individual distribution of TD (only about 50% present extremity dyskinesia and less than 25% facial, head and trunk dyskinesia, independent of the severity of the syndrome). Finally, convergent validity was found between the SHRS hyperkinesia scale and AIMS and divergent validity between all of the other scales.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Side effects of hybrid liver support therapy: TNF-alpha liberation in pigs, associated with extracorporeal bioreactors.

During acute liver failure, hybrid liver support therapy could serve as a bridge to liver transplantation. In this desired temporary use, immune competent cell responses, such as the production of cytokines, might be of limiting relevance. We have investigated the Tumor Necrosis Factor-alpha (TNF) liberation in two models using pigs, connected with an extracorporeal bioreactor with homologous hepatocytes: TNF liberation was measured in arterial plasma during a 4 day perfusion time in untreated animals, model (i), and during short term perfusion of hepatectomized pigs in model (ii). Animals four days after catheter implantation in model (i) had TNF values of < 5 pg/ml. After connecting the system without hepatocytes, TNF rose to 9.7 +/- 2 within 120 min and rose further to 32.6 +/- 6 pg/ml within 4 hours after filling the system with the homologous hepatocytes. After 24 hours of continuous perfusion and during four days of perfusion, the TNF levels were lowered to baseline levels. In model (ii), TNF rose to 220 +/- 130 pg/ml within 180 min and decreased to 110 +/- 10 pg/ml within six hours, whereas controls without hepatocytes showed mean levels with a maximum of 120 +/- 20 pg/ml. In both models, there was no correlation between TNF levels and clinical abnormalities such as fever or shock symptoms. There is evidence for an activation of blood cells during experimental extracorporeal hybrid support. No typical side effects were, however, observed. Thus, TNF mediated extracorporeal cell activation does not appear to limit the application of homologous hybrid liver support therapy.

Animals↗
PubMed1992

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↗
PubMed1992

Clozapine and D1/D2 antagonism in extrapyramidal functions.

One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side-effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia.

Animals↗
PubMed1991

Perphenazine decanoate and cis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients. Serum levels at the minimum effective dose.

Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long-term maintenance treatment of schizophrenia.

Adult↗