Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients

Summary. 72 consecutive patients with suspected parkinsonian syndromes (PS) were studied by dopamine transporter (DAT) and D2 receptor SPECT in order to evaluate the accuracy of combined SPECT imaging. In the follow-up, the patients were diagnosed as having Parkinsons disease (PD, n=25), dementia with Lewy bodies (DLB, n=6), multiple system atrophy (MSA, n=13), progressive supranuclear palsy (PSP, n=8), corticobasal degeneration (CBD, n=9), and essential tremor (ET, n=11). Using the iteratively estimated optimal cutoffs, DAT was reduced in 57/61 PS patients, whereas all ET patients were identified as normal. Reduced D2 receptor binding had 7/13 patients with MSA, 6/8 patients with PSP, 2/9 patients with CBD and no ET, PD or DLB patients. FP-CIT SPECT allows an accurate detection of nigrostriatal affection in neurodegenerative PS. IBZM SPECT is useful to approve the diagnosis of PSP and MSA although a normal finding cannot exclude an atypical PS. IBZM SPECT seems to be of restricted value in CBD.     

Aminoglutethimide but not spironolactone enhances the anticonvulsant effect of some antiepileptics against amygdala-kindled seizures in rats

Summary. Aminoglutethimide (AGLD, an inhibitor of adrenal steroid synthesis) up to 5mg/kg and spironolactone (SPIR, a mineralocorticosteroid antagonist and a weak antiandrogen) up to 50mg/kg did not affect any seizure parameter in amygdala-kindled rats. AGLD (10mg/kg) significantly reduced seizure activity in rats of both gender. The combination of AGLD (5mg/kg) with phenobarbital (PB, applied at its subeffective dose of 15mg/kg) significantly shortened motor seizure and afterdischarge duration in amygdala-kindled seizures. The combined treatment of AGLD (5mg/kg) and clonazepam (CLO) at its subeffective dose of 0.01mg/kg caused significant reduction of the seizure severity, seizure duration and afterdischarge duration. Finally, AGLD (5mg/kg) proved ineffective upon the action of valproate (VPA) in this model of epilepsy. In contrast to AGLD, SPIR (50mg/kg) did not affect the action of PB, CLO or VPA against kindled seizures in rats. AGLD did not alter the free plasma levels and brain concentration of PB or CLO, so a pharmacokinetic interaction does not seem probable. Among a variety of chemoconvulsants, bicuculline and N-methyl-D-aspartic acid reversed the effects of AGLD/PB and AGLD/CLO combinations. Aminophylline, kainic acid, strychnine and the glucocorticosteroid (hydrocortisone) were ineffective in this respect. Our data confirm the hypothesis that AGLD-mediated events may play a role in seizure activity and can affect the anticonvulsant activity of some conventional antiepileptic drugs against kindled seizures. Moreover, extrapolation of obtained results to clinical practice may indicate that patients with complex partial seizures may be safely co-medicated with AGLD or SPIR without the risk of worsening of seizure control.     

Homocysteinemia in psychiatric disorders: association with dementia and depression,but not schizophrenia in female patients

Summary. Homocysteinemia has been reported to be a risk factor for dementia, depression and also schizophrenia, the latter in a gender-specific manner. We have determined homocysteine in female inpatients suffering from various psychiatric diseases to further investigate a possible association between homocysteinemia and psychiatric disorders. Homocysteine was not elevated in schizophrenic females (mean, 11.6±5.8µmol/l); in accordance with previous studies, homocysteinemia could be found frequently in dementia of different aetiology (mean, 17.2±6.7µmol/l), but also to a slighter extent in depressive disorders (mean, 12.9±3.8µmol/l), especially in elderly subjects. We thus suggest that homocysteinemia, at least in females, is an unspecific risk factor for organic brain disorders, but not endogenous psychoses.     

Über die sogenannte „zentrale Tonusdifferenz“ mit Nystagmusbereitschaft nach einer Seite

Zusammenfassung An Hand von 71 sowohl otologisch als auch neurologisch-psychiatrisch untersuchten Fällen wird zur Frage der sog. zentralen Tonusdifferenz Stellung genommen.1. In 40% der Beobachtungen waren als Ursache des einseitigen Nystagmusüberwiegens Schäden im Labyrinth bzw. im Bereich des 1. vestibulären Neurons anzunehmen.2. Bei 35% der Untersuchten war sowohl eine periphere als auch zentrale Verursachung möglich. Überwiegend handelt es sich um Patienten mit einem klinischen Halswirbelsäulensyndrom. Der funktionelle Charakter der Störung wird diskutiert.3. In 25% unserer Fälle lagen sicher zentrale Schäden vor, jedoch fand sich mit 2 Ausnahmen kein Anhalt für die Annahme einer Hirnstammläsion als Ursache der Nystagmusbereitschaft nach einer Seite.Therapieversuche werden erwähnt.Der Begriff zentrale Tonusdifferenz wird als mißverständlich abgelehnt und betont, daß dem einseitigen Nystagmusüberwiegen keineswegs ein Hinweischarakter auf eine Hirnstammcontusion zukommt. Die Nystagmusbereitschaft nach einer Seite kann von jedem Abschnitt des vestibulären Systems ausgelöst werden.Teilergebnis eines Forschungsauftrages des Bundesministeriums für Arbeit.     

A new low-dose formulation of selegiline: clinical efficacy,patient preference and selectivity for MAO-B inhibition

Summary. Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption Zydis Selegiline. The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25mg or 10mg) with conventional selegiline hydrochloride tablets conventional selegiline tablets (10mg) in patients with Parkinsons disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10mg (n=68), or to treatment with Zydis Selegiline 1.25mg (n=64) or Zydis Selegiline 10mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25mg or conventional selegiline tablets 10mg for 14–16 days in an open-label, randomised parallel group study.Both Zydis Selegiline (1.25mg and 10mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10mg based on comparison of mean total Unified Parkinsons Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range ±5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25mg and conventional selegiline tablets 10mg was –2.50 (–4.84, –0.17), and for Zydis Selegiline 10mg and conventional selegiline tablets 10mg, 0.04 (–2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25mg, –2.14 (–3.94, –0.33) and Zydis Selegiline 10mg, –0.90 (–2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01).In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001).Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25mg (90%) or Zydis Selegiline 10mg (86%) over conventional selegiline tablets 10mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25mg liked the taste compared with 45% taking Zydis Selegiline 5mg (in the previous study).Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25mg. In contrast, after 14 days treatment with conventional selegiline tablets 10mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400mg to 200mg.In summary, Zydis Selegiline at doses of 1.25mg and 10mg was therapeutically equivalent to conventional selegiline tablets 10mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine.Present address: Cephalon UK Ltd., Surrey Research Park, Guildford, United KingdomPresent address: Safetymednet, Ruscombe, United KingdomPresent address: Oxford Glycosciences (UK) Ltd., Abingdon, United KingdomReceived December 3, 2002; accepted July 23, 2003     

Spatial correlations between the neuronal inclusions, swollen achromatic neurons, and glial cells in neuronal intermediate filament inclusion disease (NIFID)

Summary. Neuronal intermediate filament (IF) inclusion disease (NIFID) is characterized by neuronal loss, neuronal cytoplasmic IF-positive inclusions (NI), swollen neurons (SN), and a glial cell reaction. We studied the spatial correlations between the clusters of NI, SN, and glial cells in four gyri of the temporal lobe (superior temporal gyrus, inferior temporal gyrus, lateral occipitotemporal gyrus, and parahippocampal gyrus) in four cases of NIFID. The densities of histological features (per 50×250µm sample field) were as follows: NI (mean=0.41, range 0.28–0.68), SN (mean=1.41, range 0.47–2.65), glial cell nuclei (mean=5.21, range 3.63–8.17). The NI and the SN were positively correlated in half of the brain regions examined, the correlations being present at the smallest field size (50×250µm). The NI were also positively or negatively correlated with the glial cell nuclei in different areas, the negative correlations being present at the smallest field size. Glial cell nuclei were positively or negatively correlated with the SN in different brain areas, mainly at the larger field sizes (400×250 and 800×250µm). The spatial correlation between the clusters of NI and SN in the cortex suggests their development within the same columns of cells. At first, the glial cell reaction is also confined to these columns but later becomes more generally distributed across the cortex.     

Mental Hygiene of the Special Schools Teachers in Kerman,Iran

The goal of this research is to identify and study the mental hygiene and its related factors (individual, family, organizational) in the Kerman special schools teachers. 266 teachers of the special schools of the cities of the province Kerman were chosen as the research sample. The necessary data were obtained by questionnaire which its validity and reliability were determined. The statistical analysis of the research findings (by Spearman coefficient test) Man-Whithey and Kruskal wallis tests showed that there was a positive and meaningful relationship between Level of education, service of record the number of the members of teachers family, income, dwelling-place, economic power, acceptance of the teachers job in their family, leadership style, suitable educational possibilities, suitable educational space, job satisfaction with the mental hygiene of the teachers. The results of the research also showed that the Kerman special schools teachers enjoyed a relatively desirable mental hygiene.     

Apurulent bacterial meningitis (compartmental leucopenia in purulent meningitis)

Summary Meningococci and Haemophilus influenzae may invade the subarachnoid space during the bacteriaemic phase without impairment of the blood-CSF barrier and in the absence of any leucocyte reaction. In pneumococcal meningitis the CSF may also contain less than 100 cells/l despite the presence of pure bacterial cultures, but the barrier is completely broken when the serum/CSF concentration ratio is below 10. A clinical analysis of eight patients with fewer than 100 cells/l revealed that the first symptoms of meningitis appeared at least 3 days prior to the diagnostic lumbar puncture. There was a strong neutrophilic reaction in the blood with a prevalence of juvenile forms in most cases, indicating intact antibacterial defence mechanisms. Within 24 h after the start of antibiotic therapy the cell number rose above 2000/l accompanied by disappearance of pneumococci. Six of the eight patients died. In three cases autopsy revealed thick layers of pus over the convexities, indicating a compartmental separation of the ventricles and the spinal subarachnoid space. In one case of late diagnosed bacterial meningitis with a pleocytosis of 430/l the CSF lysozyme level was seven times higher than compatible with this cell number. Hyperphagocytosis and cellular disintegration is thought to cause the leucopenia within the spinal CSF compartment. Apurulent bacterial meningitis can be seen as a disease entity that is a diagnostic pitfall and also a prognostic sign.     

Low temperature in the golden hamster accelerates the gonadal atrophy induced by short photoperiod but does not affect the daily pattern of melatonin secretion

Summary Male golden hamsters were exposed to short photoperiod at either 20C or 5C. After 4 weeks a complete gonadal inhibition was observed in animals kept at 5C while in animals kept at 20C such an inhibition was much less. No significant difference in the pattern of pineal and plasma melatonin concentrations was observed between hamsters kept at 20C and 5C. If in the golden hamster pineal melatonin secretion is implicated in the transduction of the photoperiodic information, it is probably not implicated in the transduction of thermal information.     

Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism

Summary. Higher plasma homocysteine concentrations can influence genomic DNA methylation in peripheral blood cells. In the present controlled study we observed a significant increase (10%) of genomic DNA methylation in patients with alcoholism (t=–3.16, df=158, p=0.002) which was significantly associated with their elevated homocysteine levels (multiple linear regression, p<0.001). Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control these patients.D.B. and B.L. contributed equally to this work     

Ideomotor apraxia in patients with dementia of alzheimer type

Summary Ideomotor apraxia was checked in a carefully selected group of patients with Alzheimer's dementia, all in the mild stage of the disease. It was shown that ideomotor apraxia is not an early neuropsychological feature. When compared with other cognitive measures, the speed of deterioration of ideomotor apraxia appears to be particularly slow.Study supported by grant from the Consiglio Nazionale delle Ricerche (No. 8001829). Preliminary data presented at the XXIV Annual Meeting of the Italian Neurological Society (Pisa, October 1985)     

A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition

Summary. Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption Zydis Selegiline (1.25–10mg) with conventional selegiline hydrochloride tablets conventional selegiline tablets (10mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as -phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96mg) of a 10mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC_0–) values following Zydis Selegiline 10mg (5.85 [7.31] ng·h/mL) were approximately five times higher than those following conventional selegiline tablets 10mg (1.16 [1.05] ng·h/mL). In contrast, plasma concentrations of metabolites were significantly (p<0.001) lower following Zydis Selegiline 10mg than following conventional selegiline tablets 10mg.Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25–5mg. Bioavailability was determined using AUC and peak plasma concentrations (C_max). The C_max of selegiline was similar following administration of Zydis Selegiline 1.25mg (1.52ng/mL) or conventional selegiline tablets 10mg (1.14mg/mL). The range of values for AUC_0– and C_max following Zydis Selegiline 1.25mg were entirely contained within the range following conventional selegiline tablets 10mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25mg (1.19, 0.34, 0.93ng/ml, respectively) than after conventional selegiline tablets 10mg (18.37, 3.60, 12.92ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC_(0–t) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25mg and conventional selegiline tablets 10mg (13.0µg versus 17.6µg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25mg or conventional selegiline tablets 10mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10mg group than in the Zydis Selegiline 1.25mg group after repeated administration over 13 days.In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10mg, Zydis Selegiline 1.25mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinsons disease.Present address: Cephalon UK Ltd., Surrey Research Park, Guildford, United KingdomPresent address: Biogen Ltd., Maidenhead, Berks, United KingdomPresent address: Safetymednet, Ruscombe, United KingdomPresent address: Oxford Glycosciences (UK) Ltd., Abingdon, United KingdomPresent address: Pfizer UK Ltd., High Wycombe, United KingdomReceived December 3, 2002; accepted June 30, 2003     

Cytoplasmic and axoplasmic density variations in relation to hyperactivity

Summary The density of the cytoplasm and axoplasm of the anterior horn cell in rats was determined by X-ray microradiography. The average density of the cytoplasm of more than 400 cells from control rats was 0.31 g/³, while that of over 600 cells from rats fed IDPN (- iminodipropionitrile) was 0.43 g/³.Hyperactivity developed during the first 5 weeks and was associated with a gradual increase in cytoplasmic density to 0.51 g/³.At 6 weeks there was a drop in density to 0.36 g/³ which coincided with the appearance of axonal balloons having a density of 0.17 g/³.During the 7–12th week on the diet, the cytoplasmic density showed a gradual increase to 0.59 g/³ and the balloons to 0.29 g/³.The volume of the nerve cells remained fairly constant. The density increases were discussed in relation to hypertrophy, dystrophy, and hyperactivity.

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Zusammenfassung Die Dichte des Cytoplasmas und Axoplasmas der Vorderhornzellen von Ratten wurde durch Röntgenmikroradiographie bestimmt. Die mittlere Dichte des Cytoplasmas von mehr als 400 Zellen der Kontrollratten war 0,31 g/³, während die mittlere Dichte von mehr als 600 Zellen der Ratten, die mit IDPN (- iminodipropionitrile) gefüttert waren, 0,43 g/³ war.Hyperaktivität entwickelte sich während der ersten 5 Wochen und war mit einer progressiven Zunahme der Cytoplasmadichte bis auf 0,51 g/³ verbunden.Nach 6 Wochen sank die Dichte auf 0,36 g/³. Diese Tatsache traf mit dem Auftreten der Axonauftreibungen zusammen, die eine Dichte von 0,17 g/³ hatten.Nach 7–12 Wochen zeigte die Cytoplasmadichte eine progressive Zunahme auf 0,59 g/³ und die der Auftreibungen eine Zunahme auf 0,29 g/³.Das Volumen der Nervenzellen blieb ziemlich konstant.Die möglichen Zusammenhänge zwischen Zunahme der Dichte, Hypertrophie, Dystrophie und Hyperaktivität werden dargestellt.

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Supported by U. S. Public Health Grant NB 1305.     

The yield of laboratory investigations in children with infantile autism

Summary. Purpose: To evaluate the yield of laboratory investigations in infantile autism. Methods: We retrieved and evaluated the results of investigative procedures recorded in the medical files of autistic infants in four child developmental centers and two pediatric psychiatric outpatient clinics. Results: One-hundred and thirty-two infants were included in the study of whom 47 (36%) underwent autistic regression at an average age of 20 months. The investigative procedures included electroencephalogram (n=132), neuroimaging (n=70), genetic studies to detect Fragile-X (n=59) and a metabolic workup (n=53). Except for the molecular diagnosis that revealed Fragile-X syndrome in two children (3%), all other tests were negative. The two infants with the Fragile-X syndrome belonged to the non-regressive group. Conclusions: The only investigative study that contributed to the diagnosis of autistic infants was the molecular diagnosis detecting Fragile-X. In spite of the high frequency of epilepsy and epileptiform abnormalities in the electroencephalograms of autistic children in general, the contribution of epilepsy, both clinical and subclinical, to the etiology of autism is apparently minimal.     

Effects of riluzole on combined MPTP + 3-nitropropionic acid-induced mild to moderate striatonigral degeneration in mice

Summary. We investigated the potency of riluzole, an anti-glutamatergic drug, to affect ongoing neuronal death process following combined MPTP+3-nitropropionic acid (3-NP) intoxication producing combined striatal and nigral degeneration (SND) in mice. We used a neuronal rescue strategy by administering riluzole after the end of intoxication. The motor disorder, its recovery, behavioral performances at motor and sensorimotor integration tasks and histopathological outcome were compared in the saline and riluzole groups (10mg/kg and 20mg/kg), matched by triplets for motor severity. While riluzole did not produce any effect on the gross motor disorder nor on rotarod task, open-field kinetic variables or on the traversing beam task, it had a subtle effect on the performances at the pole test. The histopathological outcome was significantly better in the riluzole-treated mice regarding both nigral and dorsolateral striatal cell loss and astroglial activation, with a dose-effect relationship. Thus, riluzole has limited neuronal rescue properties from an histopathological point of view with a subtle motor behavior improvement in a MPTP+3-NP-induced SND in mice.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Treatment recommendations for psychiatric outpatients

Summary Choosing the proper match between patient and modality of psychiatric treatment has received little attention. This study examines factors associated with recommendations for particular treatment modalities for 110 out-patients (34% male, 66% female; mean age 35.2years). We usedfour mutually-exclusive categories of treatment recommendations: individual psychotherapy alone, other psychosocial therapies (e.g., group therapy, family therapy) with or without individual therapy, psychotropic drugs in combination with one or more psychosocial approaches (the drugs-plus group), and psychotropic drugs alone. Dependent variables included patient self-ratings of symptoms (both as single symptoms and as symptom clusters), interviewer mental status ratings, estimates of social dysfunction, the course of the illness over time, the prognosis, an estimate of the patient's willingness to follow the treatment plan, and a recommendation about various types of family contact or intervention. The drugs-plus group was the most severely ill, as reflected both by patients' selfratings and by interviewer ratings. The drugs-alone group showed the least distress on both subjective and observational measures, and was the oldest and best-educated of the four groups. This finding on education shows that drugs-alone is not viewed as second-class treatment, to be given to the uneducated. Despite less distress and less social dysfunction in the drugs-alone group, this group was judged far more likely to need psychiatric hospitalization if the treatment plan were not followed, suggesting that this group was, potentially, the sickest of the four.Comparison of the drugs-plus and drugs-alone groups confirmed the finding in the four-way comparisons that the drugs-plus group was, at the time of the evaluation, in more distress than the drugs — alone group. This was especially true with regard to self-ratings; the patient's subjective distress may be a strong determinant of the decision to add a psychosocial approach in patients for whom drugs are indicated. Surprisingly, there were no significant differences between patients thought to need individual psychotherapy, and those thought to need other psychosocial approaches. We conclude that while clinicians do seem to have criteria for deciding whether the drug needs to be accompanied by some form of psychosocial therapy, they do not seem to have criteria (within the limitations of our measuring instruments) for deciding between individual psychotherapy alone and other psychosocial approaches.

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Zusammenfassung Der Auswahl der einem Patienten angemessenen psychiatrischen Behandlungs-methode wurde bisher wenig Aufmerksamkeit geschenkt. In dieser Arbeit werden die Faktoren untersucht, die mit den Empfehlungen bestimmter Behandlungsarten für 110 ambulante Patienten (34% Männer, 66% Frauen, mittleres Alter 35, 2 Jahre) einhergehen. Wir benutzten vier sich gegenseitig ausschließende Kategorien für Behandlungsempfehlungen: ausschließlich individuelle Psychotherapie, oder psychosoziale Therapien (z. B. Gruppentherapie, Familientherapie) mit oder ohne individueller Psychotherapie, Psychopharmaka kombiniert mit einem oder mehreren psychosozialen Therapieverfahren (die drugs-plus-Gruppe), sowie ausschließ-lich Medikamente. Die abhängigen Variablen umfaßten eine Selbsteinschätzung der Patienten bezüglich ihrer Symptome (sowohl einzelne Symptome wie Symptomverbände), eine Einschätzung des psychischen Zustands durch den Interviewer, die Beurteilung der sozialen Störung, den Krankheitsverlauf, die Prognose, die Einschätzung der Gewilltheit des Patienten, dem Behandlungsplan Folge zu leisten, und eine Empfehlung verschiedener Formen von Familienkontakt oder Intervention. Die Gruppe, die Medikamente und psychosoziale Behandlungen erhielt, war am schwersten krank, das spiegelte sich sowohl in der Selbsteinschätzung der Patienten wie auch in der Beurteilung durch den Interviewer wieder. Die Gruppe die nur Psychopharmaka erhielt, zeigte sowohl bei den subjektiven wie bei den objektiven Meßverfahren die geringsten Beschwerden, sie wies den höchsten Altersdurchschnitt und das höchste Erziehungsniveau unter den vier Gruppen auf. Dieses letzte Ergebnis zeigt, daß die Behandlung mit Psychopharmaka nicht als eine zweitklassige angesehen wird, die sich für Ungebildete eignet. Trotz geringerer Beschwerden und geringerer Störungen in der ausschließlich medikamentös behandelten Gruppe, schätzte man, daß diese Gruppe weitaus eher psychiatrische Hospitalisierung braucht, wenn der Behandlungs-plan nicht eingehalten wird. Das deutet darauf hin, daß diese Gruppe potentiell die kränkste unter den vieren war. Der Vergleich der Gruppe, die Medikamente und psychosoziale Behandlungen erhielt, mit der, die nur Medikamente erhielt, bestätigte das Ergebnis aus den vierfachen Vergleichen, daß die drugs-plus-Gruppe zum Zeitpunkt der Bewertung mehr litt als die drugs-alone-Gruppe. Das zeigte sich besonders deutlich bei den Selbsteinschätzungen; das subjektive Leiden des Patienten kann einen starken Druck auf die Entscheidung ausüben, eine psychosoziale Behandlungsmethode bei Patienten zusätzlich anzuwenden, für die Medikamente indiziert wären. Überraschenderweise gab es keine signifikanten Unterschiede zwischen Patienten, bei denen man individuelle Psychotherapie für notwendig hielt und solchen, bei denen man andere psychosoziale Methoden für angezeigt hielt. Wir ziehen daraus den Schluß, daß Kliniker, obwohl sie allem Anschein nach Kriterien für die Entscheidung haben, ob die medikamentöse Behandlung von irgendeiner Form psychosozialer Therapie begleitet werden soll, offenbar keine Kriterien (in den Grenzen unserer Meßinstrumente) für die Entscheidung zwischen ausschließlicher Einzelpsychotherapie und anderen psychosozialen Verfahren haben.

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Résumé On s'est peu penché sur le problème de la correspondance spécifique entre le patient et la modalité de traitement psychiatrique choisie. Dans cette étude, on examine les facteurs qui sont liés à l'indication de modalités de traitement particulières chez 110 patients ambulatoires (34% d' hommes, 66% de femmes; âge moyen: 35,2 ans). Nous avons utilisé quatre catégories, s'excluant mutuellement, d'indications thérapeutiques: psychothérapie individuelle seule, autres thérapies psychosociales (par exemple thérapie de groupe, thérapie de famille), avec ou sans thérapie individuelle, médicaments psychotropes combinés avec une ou plusieurs approches psychosociales (groupe médicaments combinés), et médicaments psychotropes seuls. On a établi un ensemble de variables qui comprenait: l'appréciation des symptômes par le patient lui-même (aussi bien des symptômes pris individuellement que de ceux-ci dans leur ensemble), l'appréciation du status psychique par l'examinateur, l'estimation de la désadaptation sociale, l'évolution de la maladie dans le temps, le pronostic, l' appréciation de la volonté du patient de suivre le plan thérapeutique, et une recommandation concernant différents types de contact ou d'intervention familiale. Le groupe médicaments combinés était le plus gravement malade, ce qui se reflétait à la fois dans les appréciations des patients eux-mêmes et dans les appréciations des examinateurs. Selon ces deux mêmes mesures (du patient et de l'observateur), c'est le groupe médicaments seuls qui montrait le moins de détresse; c'était le groupe le plus ágé et le mieux éduqué des quatre. Cette donnée concernant l'éducation montre que la thérapie médicamenteuse seule n'est pas considérée comme un traitement de seconde classe destiné à ceux qui n'ont pas repu d'éducation. Malgré une détresse et une désadaptation sociale moindres, on a jugé que le groupe médicaments seuls était de loin le plus susceptible de devoir recourir à une hospitalisation psychiatrique si le plan thérapeutique n'était pas suivi; ceci implique que ce groupe serait, en puissance, le plus malade des quatre. La comparaison des groupes médicaments combinés et médicaments seuls a confirmé le résultat des comparaisons entre les quatre groupes, à savoir que le groupe médicaments combinés était, au moment de l'examen, dans un état de détresse plus grand que le groupe médicaments seuls. Cela était particulièrement vrai par rapport aux auto-appréciations; la détresse subjective du patient peut donc être un facteur déterminant important dans la décision d'adjoindre une approche psychosociale dans les cas où une thérapie médicamenteuse est indiquée. Nous avons été surpris de constater qu'il n'y avait pas de différences significatives entre les patients pour lesquels on avait indiqué une psychothérapie individuelle et ceux pour qui on avait indiqué d'autres approches psychosociales. Nous en concluons que si les cliniciens semblent avoir des critères leur permettant de décider si oui ou non la thérapie médicamenteuse doit être accompagnée d'une forme quelconque de thérapie psychosociale, ils semblent par contre ne pas en avoir (dans le cadre des limites de nos instruments de mesure) lorsqu'il s'agit de choisir entre la psychothérapie individuelle seule et d'autres approches psychosociales.

     

Influence of transcutaneous nerve stimulation (TNS) on acute pain

Summary Using transcutaneous nerve stimulation (TNS) simple surgical procedures such as tooth extractions and nerve biopsies can be performed without the usual anesthetics.Estimation of threshold and suprathreshold intensities of painful electrical stimuli show no significant change during TNS. Only the threshold for non-painful electrical stimuli is slightly increased. Cortical potentials evoked by electrical peripheral nerve stimulation are not significantly modulated by TNS. Latencies of the early components 0, I–III are unchanged, the amplitudes only slightly reduced.These observations are in contradiction to the gate-control theory of pain.Supported by Sonderforschungsbereich Hirnforschung und Sinnesphysiologie (SFB 70) der Deutschen Forschungsgemeinschaft (DFG) and Bundesminister für Arbeit und Sozialordnung, Bonn-Bad Godesberg, Federal Republic of Germany     

Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET study shows increased D2 receptors

Summary. We investigated the integrity of striatal dopaminergic system in seven patients with dopa-responsive dystonia (DRD). Dopamine transporter function ([¹¹C]CFT) and D1 ([¹¹C]NNC 756) and D2 receptors ([¹¹C]raclopride) were studied in same patients using positron emission tomography. Compared to age-adjusted control values the dopamine D2 receptor availability was increased in DRD. The mean age-adjusted [¹¹C]raclopride uptake was 116% of the control mean in the putamen (p=0.004) and 114% in the caudate nucleus (p=0.007). The mean [¹¹C]NNC 756 uptake was not different between DRD patients and controls, the age-adjusted uptake in DRD being 93% of mean control value in the putamen (p=0.20) and 95% in the caudate nucleus (p=0.40).The dopamine transporter binding was not altered. The [¹¹C]CFT uptake in DRD was 96% of the control value in the putamen (p=0.64), and 95% in the caudate nucleus (p=0.44).In conclusion, striatal dopamine D2 receptors availability is increased in DRD whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinsons disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine or a compensatory response to dopamine deficiency, or both.     

The protein composition of myelin in multiple sclerosis (MS) and orthochromatic leukodystrophy (OLD)

Summary In 4 cases of MS, in which the progression of disease differed, and in one case of infantile OLD the proteins of a homogenate and a myelin fraction with and without plaques were separated electrophoretically with polyacrylamide gels in a buffer system of phenol/formic acid/water. The relation of proteolipid protein to basic protein was estimated planimetrically and compared with control cases.In myelin from plaque material of chronic running MS cases an average decrease of 41% in basic protein was observed, while in an acute progressing case no obvious alterations could be discerned. Myelin from apparently normal MS white matter showed an average decrease of 13% in basic protein. The results of the OLD case were similar to those obtained from the chronic MS cases. The decrease of basic protein (chronic MS, OLD) was markedly more in the homogenate fraction than in the purified myelin. In a control case with autolytic alterations (autopsy after 24 hours) the content of basic protein was also diminished.Our findings indicate that the reduction of basic protein in myelin is a non-specific effect in demyelinating diseases.Presented in part at the Third International Meeting of the International Society for Neurochemistry, July 5–9th, 1971, Budapest.Supported by Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 33), Stiftung Volkswagenwerk, and Forschungsmittel des Landes Niedersachsen.