Design and subjects of a Finnish epidemiological study on psychiatric disorders in childhood

In an epidemiological multi-centre study, parents filled in the Rutter Parent Questionnaire (RA2) and teachers filled in the Rutter Teacher Questionnaire (RB2) for almost 6000 children. The children filled in the Children's Depression Inventory (CDI). The subjects well represented the entire population of 8-9-year-old children in Finland. The material and design of the study as well as the basic demographic characteristics are presented.     

Evidence for opiate-activated NMDA processes masking opiate analgesia in rats

The acute interaction between opioid receptors and N-methyl-D-aspartate (NMDA) receptors on nociception was examined in rats using tail-flick and paw-pressure vocalisation tests. When injected at various times (1 to 6 h) after morphine (5 to 20 mg/kg, i.v.) or fentanyl (4x40 microgram/kg, i.v.), the opioid receptor antagonist naloxone (1 mg/kg, s.c.) not only abolished the opiate-induced increase in nociceptive threshold, but also reduced it below the basal value (hyperalgesia). The noncompetitive NMDA receptor antagonist MK-801 (0.15 or 0.30 mg/kg, s.c.) prevented the naloxone-precipitated hyperalgesia and enhanced the antinociceptive effects of morphine (7.5 mg/kg, i.v.) and fentanyl (4x40 microgram/kg, i.v.). These results indicate that the antinociceptive effects of morphine and fentanyl, two opiate analgesics widely used in humans in the management of pain, are blunted by concomitant NMDA-dependent opposing effects which are only revealed when the predominant antinociceptive effect is sharply blocked by naloxone. This study provides new rationale for beneficial adjunction of NMDA receptor antagonists with opiates for relieving pain by preventing pain facilitatory processes triggered by opiate treatment per se.     

Enhanced ornithine decarboxylase activity is associated with attenuated rate of damage evolution and reduction of infarct volume in transient middle cerebral artery occlusion in the rat

Ornithine decarboxylase (ODC) transgenic and alpha-difluoromethyl ornithine (DFMO)-treated rats were exposed to transient middle cerebral occlusion (MCAO) to examine the role of intraischaemic ODC-activity on the evolution of ischaemia-reperfusion damage. Magnetic resonance imaging (MRI) data show that the damage develops slower in ODC transgenic than in DFMO-treated rats, which is not caused by a difference in perfusion. Furthermore, infarct volumes are smaller in the former animals one day later. These data support the idea of endogenous neuroprotective action of ODC.     

A photothrombotic ring stroke model in rats with or without late spontaneous reperfusion in the region at risk

This study aimed at developing a dual setup of the photothrombotic ring stroke model with or without late spontaneous reperfusion in the region at risk and to explore the morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser-irradiation beam (o.d. 5.0 mm, 0.35 mm thick) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion. Transcardial carbon-black perfusion revealed that a laser intensity of 0.90 W/cm(2) resulted in late, that is, starting at 72 h, spontaneous reperfusion, whereas the lowest laser intensity that produced lack of reperfusion at 7 days post-irradiation was 1.84 W/cm(2). Laser-Doppler flowmetry showed prompt cortical cerebral blood flow (cCBF) reduction both in the ring lesion and region at risk (12% and 25% of control values) after high-intensity irradiation; these reduced flow values were more rapid and pronounced than in the low-intensity irradiation setup as previously shown. The high- compared with low-intensity irradiation setup produced more frequent occurrence of thrombi in the ring-lesion region and a larger ischemic cortical lesion with a more rapid pace of ischemic cellular changes in the ring-lesion region and the region at risk. The region at risk transformed into pannecrosis in the high-intensity, but recovered morphologically in the low-intensity irradiation setup. This dual photothrombotic setup with or without spontaneous reperfusion enables the study of events related to ischemic cell survival or death in an anatomically predefined region at risk.     

Insulin-like growth factor-1 (IGF-1)-induced inhibition of growth hormone secretion is associated with sleep suppression

The hypothalamic growth hormone (GH)-releasing hormone (GHRH) promotes non-rapid eye movement sleep (NREMS). Insulin-like growth factor-1 (IGF-1) acts as a negative feedback in the somatotropic axis inhibiting GHRH and stimulating somatostatin. To determine whether this feedback alters sleep, rats and rabbits were injected intracerebroventricularly (i.c.v.) with IGF-1 (5.0 and 0.25 microgram, respectively) and the sleep-wake activity was studied. Compared to baseline (i.c.v. injection of physiological saline), IGF-1 elicited prompt suppressions in both NREMS and rapid eye movement sleep (REMS) in postinjection hour 1 in rats and rabbits. The intensity of NREMS (characterized by the slow wave activity of the EEG by means of fast-Fourier analysis) was significantly enhanced 7 to 11 h postinjection in rats. Plasma GH concentrations were measured in 30-min samples after i.c.v. IGF-1 injection in rats and a significant suppression of GH secretion was observed 30 min postinjection. The simultaneous inhibition of the somatotropic axis and sleep raises the possibility that the sleep alterations also result from an IGF-1-induced suppression of GHRH. The late increases in NREMS intensity are attributed to metabolic actions of IGF-1 or to a release of GHRH from the IGF-1-induced inhibition.     

ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain

A reliable, sensitive and specific sandwich ELISA for the quantitation of paired helical filament (PHF) tau in human brain was developed using well-defined monoclonal antibodies. We examined rapid-autopsy-derived brain tissue from 21 neuropathologically confirmed Alzheimer's disease (AD) patients and 14 nondemented controls, matched for age, sex and postmortem delay times. We demonstrated significant elevations of phosphorylated tau levels in the frontal and parietal cortex as well as in the hippocampus of AD patients as compared to the nondemented controls. No difference was observed in the cerebellum. Phosphorylated tau levels measured by ELISA were significantly correlated with the presence or absence of neurofibrillary tangles.     

Familial scapuloperoneal myopathy and mitochondrial DNA defect

The authors present 13 members of 4 generations in a family with scapuloperoneal myopathy. The disease showed autosomal dominant inheritance. In all 6 patients examined, the disease began in the third decade (18-31 years). Initially the shoulder girdle was involved, and the process slowly spread to the distal part of the lower extremities in several years or decades. The facial and pelvic muscles were only moderately involved; ocular muscle involvement was absent. Myopathy was proved by electromyography and muscle biopsy. In 1 case, electrophysiological evidence of peripheral neuropathy was found, and in 3 other patients central nervous system involvement (dementia, epilepsy) and optic atrophy complicated the syndrome. In the youngest patient, a mutation could be found in the 'hot-spot region' of the muscle mitochondrial DNA by polymerase chain reaction.     

Prevalence and incidence of clinically diagnosed memory impairments in a geographically defined general population in Sweden. The Piteå Dementia Project

In the Pite? River Valley all persons with memory impairment that interferes with normal life are referred to one hospital department for clinical workup and diagnosis. 619 patients were assessed in the department during the years 1990-1995. Of these, 36.9% had Alzheimer's disease (AD), 30.4% had vascular dementia (VaD), 3.0% had a mixed AD/VaD, 3.2% had frontotemporal dementia and 5.3% had other forms of dementia. Another 7% had memory impairment but no dementia. The overall mean annual incidence rate of clinically relevant dementia was 295/100,000 persons at risk and the mean prevalence rate was 755/100,000 persons. For persons 65 years and older the incidence and prevalence rates were 840 and 2,150/100,000 persons, respectively. This means that annually, approximately 300 persons/100,000 population over the age of 40 need medical attention or social services.     

Dissociative symptoms in obsessive-compulsive dimensions

Previous studies have described co-occurrence between obsessive-compulsive disorder (OCD) and dissociation. We intended to evaluate the phenomenological association between different obsessive-compulsive and dissociative symptoms more precisely. Seventy patients with OCD (DSM-IV) were evaluated with the Hamburg Obsessive-Compulsive Inventory (HZI) and the Dissociation Experience Scale. Correlation and discriminant analysis were performed. The dimensions 'Checking' and 'Symmetry and Ordering' were significantly related to dissociative symptomatology. A clear-cut lack of association was found in 'Washing and Cleaning', 'Counting and Touching' and 'Aggressive Impulses and Fantasies'. HZI dimensions significantly discriminated patients with high from patients with low dissociative symptomatology. Psychodynamic and therapeutical aspects of these findings are discussed. Copyright Copyright 1999 S. Karger AG, Basel     

Dose-dependent effects of noradrenergic denervation by DSP-4 treatment on forced swimming and β-adrenoceptor binding in the rat

Summary. DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals originating from the locus coeruleus. Preliminary data suggested that its effect in a typical screening test for antidepressant drugs, the forced swimming test, is biphasic dependent on the dose. In the present study, DSP-4 was administered in four doses (5, 10, 30 and 50 mg/kg) to male Wistar rats. Administration of the neurotoxin had a dose-dependent biphasic effect on immobility time in the forced swimming test 8 and 9 days later. Thus, DSP-4 at the dose of 10 mg/kg increased immobility, but higher doses reduced this measure. The reduction of noradrenaline concentration in the frontal cortex and hippocampus was dose-dependent starting from the dose 10 mg/kg. Cortical β-adrenoceptor binding was increased by DSP-4 treatment at the doses 30 mg/kg and 50 mg/kg. These results suggest that the increase in immobility time in the forced swimming test is associated with presynaptic changes in noradrenaline availability, whereas the decrease in immobility observed after more complete denervation is associated with postsynaptic receptor supersensitivity. Received September 2, 1998; accepted February 2, 1999