Biomedical subjects
Publications and source records attributed to M Dose.
The present study analyses in humans the control principles of sequential, unpracticed pointing movements in a 2-dimensional space. Our data reveal that variable pointing errors add up within such sequences. This finding supports the hypothesis that movement amplitude rather than position is the controlled variable of the investigated movements.
A recent study showed an adjuvant effect of carbamazepine in the neuroleptic treatment of acute schizophrenic psychoses. Since beclamide (beta-chlorpropionamide) was reported to reduce the neuroleptic doses required, the combination haloperidol-beclamide was tested using a double-blind, placebo-controlled study in 23 inpatients with an acute schizophrenic psychosis. In both groups patients received haloperidol and either beclamide or placebo. Every 7 d the treating psychiatrist could increase the haloperidol dose by 3 mg per day if clinically necessary. Chlorprothixene and biperiden were on hand as additional medication. After 28 d beclamide or placebo were discontinued under a constant dose of haloperidol and a final rating with the Inpatient Multidimensional Rating Scale, Brief Psychiatric Rating Scale, and Extrapyramidal Symptom Scale was carried out. Without reaching statistical significance, the beclamide group needed a lower dose of neuroleptic medication, showed fewer side effects and a more pronounced psychopathological improvement.
Process research in behavioral family therapy (BFT) is a hitherto neglected area with the notable exception of the work of Alexander and Patterson with their colleagues. However, the development of instruments to assess therapist's behavior during the treatment session seems timely for the following reasons: (a) to investigate the relationship between therapist behavior and outcome, (b) to improve therapist training/supervision, (c) to establish treatment integrity in comparative outcome studies, and (d) to monitor treatment progress. For these purposes two sets of instruments were developed: (a) a category system to describe the content of a session, which is rated every 30 seconds and (b) several rating scales to evaluate therapist behavior, including relationship competency, ability to structure a session, didactic competence, ability to initiate behavioral probes, use of appropriate intervention strategies, use of reinforcement, and dealing with uncooperativeness. Scales are described, and data on their reliability and utility are presented.
Stable attitudes towards illness and treatment and a high compliance with a 5-week low dose neuroleptic treatment (with/without anticonvulsant adjuvant therapy) were observed in 18 inpatients with schizophrenic disorders (ICD-9, DSM-III-R). Patients having previously received neuroleptics showed more compliant attitudes and greater satisfaction with the treatment, and complained less often about side effects. Noncompliant attitudes were related to dissatisfaction with treatment and self-rated depressed mood. Results of this pilot study are discussed, considering methodological problems and possible therapeutic implications.
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The effect of low-dose haloperidol combined with the anticonvulsant carbamazepine was investigated in a 5-week placebo-controlled, double-blind study in acute schizophrenic patients. Weekly ratings showed a clinically pronounced and statistically significant improvement in both the carbamazepine and placebo groups. However, the patients on carbamazepine needed less neuroleptic and anticholinergic medication and experienced fewer side effects compared to the patients on placebo. Moreover, patients in the carbamazepine group showed a clear deterioration after discontinuation of carbamazepine (but maintenance of neuroleptic medication), while the placebo group did not change after discontinuation of placebo. Concomitant treatment with carbamazepine in psychotic patients may help to reduce neuroleptic dosages and unwanted side effects.
The organic calcium antagonist verapamil in doses of 320-480 mg/day reduced manic symptomatology in seven of eight patients manifesting a manic or schizomanic syndrome in a placebo-controlled, double-blind study. The delayed onset of antimanic effects parallels the action of lithium in acute mania. Common pharmacological profiles of lithium, certain anticonvulsants, and neuroleptics with regard to calcium dependent processes are discussed.
Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs. secondary, endogenous vs. non-endogenous or unipolar vs. bipolar depression. They should reflect the same changes in central neurotransmitters (e.g. noradrenergic insufficiency and/or cholinergic hyperactivity) that were hypothesized as the cause of clinical symptoms. This view is challenged on the basis of our own neuroendocrine investigations in 317 psychiatric patients and 103 normal controls. According to these studies the abnormalities are nosologically rather unspecific. They are induced by a large variety of factors, e.g. emotional stress associated with the clinical symptomatology, weight loss due to malnutrition as a consequence of reduced appetite, medication and drug withdrawal. Stress-induced hypercortisolism appears to be the most common abnormality that may trigger other neuroendocrine dysfunctions, such as a blunted TSH response to TRH. Differences in neuroendocrine abnormalities of depressives are probably due to variations in the manifold factors influencing the hormonal axes involved, to temporal changes in hormonal patterns (e.g. one abnormality triggering another) and to individual differences in the basic activity and the responsiveness of the various axes.
The conductance increase induced by bath application of GABA has been measured in voltage-clamped stretch-receptor neurones of crayfish. A rapid conductance increase was obtained only at GABA concentrations above 3.3 X 10(-4) M. The response to lower GABA concentrations (between 10(-4) and 10(-6) M) developed slowly over 30-60 min. Repetitive application of intermediate GABA concentrations induced postsynaptic conductance changes which were progressively enhanced in their onset and magnitude. In the presence of nipecotic acid or in Na+-free Ringer solutions, the response to all GABA concentrations was rapid and constant for each concentration. The time course of inhibitory postsynaptic currents was unaffected by nipecotic acid. These results suggest the presence of a saturable GABA uptake system which limits the access of bath-applied GABA to postsynaptic receptors. This system has little if any effect on the termination of response to synaptically released GABA.
Effects of (1R, 3R, 4S, 6R, 7S, 8R, 10R)-3-piperidinomethyl-4-hydroxy - 8 - methoxy - 10 - methyl - 2,9 - dioxatricyclo[4,3,1,0(3,7)]decan (valperinol, GA 30-905) were investigated at the GABA-ergic synapse of crayfish stretch receptor. Valperinol does not affect GABA-induced changes of postsynaptic membrane conductance but reduces postsynaptic inhibition dose-dependently (10(-6)-10(-4) mol/l) and abolishes it completely at 10(-3) mol/l. The lack of direct postsynaptic effects suggests a presynaptic action of valperil. In the frog neuromuscular junction the amplitude of spontaneous and evoked endplate potentials is reduced by valperinol. Voltage-clamp investigations in neurones of Helix pomatia with mainly calcium-carried inward currents reveal a dose-dependent (10(-3)-10(-6) mol/l) inhibition of calcium inward current by valper-lyinol. These findings in preparations of three different species indicate a calcium-antagonistic action of valperinol comparable to verapamil.
The observation that opiates and endorphins exert euphorogenic effects in normal probands points to a possible involvement of endorphins in different types of affective disorders. There are several powerful arguments that the activation of particular central opiate receptors (e.g. by "opium cure", beta-endorphin, partial agonists, release of endorphins via electroconvulsion) exerts curative effects in endogenous depression. Results from a double-blind investigation of the possible antidepressant action of the opiate partial agonist buprenorphine in patients with endogenous depression revealed a strong antidepressant effect of this substance. A series of anticonvulsants, possibly acting via a GABA-ergic-like mechanism (valproate, dipropylacetamide, carbamazepine and oxcarbazepine), have recently been shown by different groups to possess antimanic and also, partially, antidepressant properties. Furthermore, a synergistic mode of action in the prophylaxis of manic episodes has been observed as concerns valproate and lithium. On the other hand, there is some evidence from both in vitro and in vivo animal experiments that chronic application of lithium results in a modification of the GABA-turnover. The present paper reviews the present state of knowledge concerning the concept of a GABA-dependent regulation of affective states.
A possible antimanic efficacy of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind, placebo-controlled ABA design. A marked improvement was observed after valproate medication in a group of 5 acutely ill manic patients. Similar results were obtained in 7 trials examining the antimanic property of the keto-derivative of carbamazepine (oxcarbazepine) in 6 patients with acute mania, whereas no antimanic effect could be observed in a treatment with diazepam and with THIP. Combination of THIP and diazepam in another patient showed a slight antimanic effect. Additionally, a possible prophylactic effect of long-term treatment using valproate was examined. In 8 of 9 patients exhibiting a bipolar affective or schizoaffective psychosis, who did not properly respond to lithium treatment, a prophylactic effect of valproate medication could be demonstrated. The results point to the view that anticonvulsants, possibly due to GABA-ergic effects, may be beneficial in affective disorders.
The conductance increase induced by GABA and structurally related compounds has been measured in voltage clamped stretch receptor neurones of crayfish. GABA induced only at 10(-3) M a rapid conductance increase. The response to lower concentrations between 10(-6) and 10(-4) M developed slowly (20-60 min). The postsynaptic conductance increase induced by repetitive application of the same GABA concentration was progressively enhanced in the speed and magnitude. In the presence of nipecotic acid or in Na+-free Ringer solutions, the response to all GABA concentrations was instantaneous and constant for each concentration. Muscimol between 10(-6) and 10(-3) M caused instantaneous dose-dependent conductance increases. These results suggest the presence of a saturable GABA uptake system limiting the access of bath applied GABA, but not of muscimol, to postsynaptic receptor sites.
During recent years alternatives to lithium prophylaxis have been developed using primary dipropylacetamide and, later on, sodium valproate, as a mono-therapy as well as in combination with low-dosage lithium treatment. It has been shown in a placebo-controlled ABA design that sodium valproate exerts an acute antimanic effect and a prophylactic action of sodium valproate has also been established. Carbamazepine represents another important contribution to the arsenal of drugs to be used as alternatives for the prophylactic treatment in patients not responding to lithium and/or experiencing too many side effects. The keto-derivative of carbamazepine, oxcarbazepine, has been shown to exert acute antimanic effects in a similar way to carbamazepine itself.