Liver trauma: a 10-year experience.

The management of 73 patients with liver trauma (58 male, 15 female; mean age 30 (range 6-68) years) presenting from January 1980 to August 1990 is reviewed. There were 29 cases of penetrating injury and 44 of blunt trauma. Seven patients were successfully managed without operation (five with blunt injury) and were discharged after a mean hospital stay of 8 days. Fifty-one cases were classified as simple injuries (grade I or II) and were managed by suture (with or without drainage) or required no intervention, with three deaths. Fifteen cases were classified as complex injuries (grade III or IV) and underwent one or more of the following: perihepatic packing, resectional debridement, hemihepatectomy and hepatotomy with direct suture ligation. Six of these patients died from uncontrolled haemorrhage. The continued use of suture for simple injuries and of resectional debridement and/or packing for complex injuries is supported. Judicious clinical assessment and radiological monitoring may reduce the number of unnecessary laparotomies.


Abdominal inflammatory myofibroblastic tumours in children.

Inflammatory myofibroblastic tumours (inflammatory pseudotumours) occurring at intra-abdominal sites in children have rarely been described. This paper reports three patients with this tumour, two of whom presented with fever, anaemia and an abdominal mass, the third with chronic duodenal obstruction. All had experienced significant weight loss. At operation, each had a large fibrous tumour (7-18 cm in diameter) originating from the transverse mesocolon, small bowel mesentery and duodenum respectively. Intraoperative frozen section histological examination in one patient was misinterpreted as a sarcoma. All the lesions were judged to have been completely excised, but one was ruptured during operation and the patient subsequently developed recurrent tumour nodules. Abdominal inflammatory myofibroblastic tumours are rare. They may be suspected before operation but their clinical, radiological and pathological features may be confused with those of malignancy. Complete excision is necessary to avoid local recurrence.


Serum tumour necrosis factor alpha and insulin resistance in gastrointestinal cancer.

Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha (TNF-alpha). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-alpha administration. In this study, insulin sensitivity and energy metabolism were measured in 11 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-alpha level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = -0.62, P = 0.003). These results suggest a possible association between endogenous TNF-alpha production and insulin resistance in patients with gastrointestinal cancer.


Psychological screening for non-specific abdominal pain.

Non-specific abdominal pain (NSAP) may have a detectable psychological component that could be used to predict outcome. To test this hypothesis, 131 patients aged 14-40 years admitted with acute abdominal pain were assessed using the General Health Questionnaire (GHQ) and Hospital Anxiety and Depression (HAD) scale, and a structured interview. Of 61 patients with NSAP, more had a psychosocial problem identified by the admitting registrar (P < 0.01) and marginally more had high questionnaire scores. The risk of having NSAP was high if an abnormality on interview accompanied high questionnaire scores (relative risk 1.93 (95 per cent confidence interval (c.i.) 1.35-2.77)) or if prodromal pain had lasted > 7 days (relative risk 2.13 (95 per cent c.i. 1.55-2.92)). After 2 years, patients with continuing pain had higher HAD and Spielberger Anxiety Trait scores (both P < 0.02); NSAP was associated with persisting pain (relative risk 2.22 (95 per cent c.i. 1.10-4.48)). Psychosocial factors are implicated in NSAP and in chronic pain, but the sensitivity and specificity of questionnaire assessment are too low to be useful in diagnosis.


Intraoperative colonoscopy in patients with colorectal cancer.

Sixty-seven patients underwent intraoperative colonoscopy during elective surgery for colorectal cancer. Complete examination of the colon was achieved in 65 patients (97 per cent), albeit with insertion through a colotomy in three (4 per cent). A synchronous carcinoma was found in six patients (9 per cent), which necessitated a change of planned surgical procedure. Synchronous polyps were detected and removed in 24 patients (36 per cent); two had polyps with carcinoma in situ. The mean age of patients with synchronous carcinoma was significantly higher than that of those without (74.1 versus 61.2 years, P = 0.02). Intraoperative colonoscopy took a mean of 15 min surgical time and only two minor complications (serosal lacerations) were encountered. In patients with colorectal cancer, intraoperative colonoscopy allows complete assessment of the colon and identifies synchronous lesions.


Anovaginal and rectovaginal fistula in patients with Crohn's disease.

Between 1971 and 1991, details of 67 women with perianal Crohn's disease were recorded prospectively using the Cardiff classification. Two groups were identified according to the presence (n = 29) or absence (n = 38) of anorectal Crohn's fistula involving the vagina. Patients in both groups were of a similar age and had had Crohn's disease for a similar period before diagnosis of perianal involvement. The incidence of associated perianal lesions, superficial ulcers, cavitating ulcers, other fistulas and strictures was not significantly different between the two groups. A greater proportion of patients with anorectal-vaginal fistulation (n = 15) had distal intestinal Crohn's disease (rectal or contiguous colorectal) compared with women with no vaginal fistulation (n = 14). A range of therapies was used to manage women with perianal Crohn's disease, from local surgery to a defunctioning stoma and/or proctectomy. Only 13 of 38 women with perianal Crohn's disease but no vaginal fistula required a defunctioning stoma or proctectomy, whereas 18 of 29 with anorectal-vaginal fistulation underwent these procedures (P < 0.05). A vaginal fistula has a considerable adverse effect on the outcome of perianal Crohn's disease.


Manual dilatation of the anus.

A group of 100 consecutive patients undergoing manual dilatation of the anus between 1980 and 1983 were reviewed retrospectively by examining the clinical presentation, diagnosis, treatment and outcome. Anal fissure was diagnosed in 46 patients, 22 had either first- or second-degree haemorrhoids, and stenosis of the anal canal was identified in seven. Manual dilatation of the anus was performed on 25 patients in the absence of a diagnosis. Dilatation failed to treat 26 anal fissures successfully. Where it was employed alone in ten cases of haemorrhoids and seven of anal stenosis, manual dilatation failed to cure seven and five patients respectively. Of the patients with no diagnosis, 23 were relieved of their symptoms following dilatation. Episodes of incontinence occurred in 27 patients, 21 of whom were female. There should be a reduced role for manual anal dilatation in the treatment of common anorectal disorders.


Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing.

Interactions between rat microglia and oligodendrocytes were examined in vitro in order to characterize the stages of adherence, phagocytosis and cytotoxicity against oligodendrocytes by microglia. Under resting conditions, microglia showed minimal contact with oligodendrocytes and exhibited surface staining of myelin basic protein and myelin debris only; they were not cytotoxic for oligodendrocytes and did not produce tumour necrosis factor (TNF). On activation with either gamma-interferon or lipopolysaccharide and interferon, these cells increased surface binding for myelin basic protein, showed greater contact with living oligodendrocytes and produced TNF in both secreted and cell surface bound forms. Secreted TNF was capable of killing oligodendrocytes but the cell surface bound form did this more efficiently. In the presence of complement, activated microglia showed significant phagocytosis of myelin basic protein which was not obvious in the unactivated cells. These results suggest that activated microglia in the presence of complement are sufficient to kill and phagocytose the oligodendrocyte-myelin complex in vitro.


Transient cellular expression of gamma-interferon in myelin-induced and T-cell line-mediated experimental autoimmune neuritis.

This study reports the cellular localization of gamma-interferon (gamma-IFN) in nerve roots during the course of experimental autoimmune neuritis induced either by active immunization (EAN) or adoptive transfer of P2-specific T-cells (AT-EAN). One micrometre thick cryosections of ventral roots of EAN and AT-EAN animals were labelled with the monoclonal antibodies DB-1 and DB-12 recognizing different epitopes of rat gamma-IFN. In EAN numerous gamma-IFN-positive cells were present before overt clinical signs and demyelination (days 11-13 after immunization). Concomitantly, raised gamma-IFN levels were measured in the serum of these animals. However, systemically increased gamma-IFN serum levels were not specific for a neuritogenic T-cell response. At subsequent stages when many axons were demyelinated (day 16 and later) gamma-IFN-positive cells had disappeared and gamma-IFN serum levels returned to normal value. gamma-Interferon positive cells could be identified as W3/13 positive T-cells and polymorphonuclear leukocytes. Additionally, a considerable number of ED1-positive macrophages showed gamma-IFN immunoreactivity. The majority of macrophages and all Schwann cells were gamma-IFN negative. Similar results were obtained in AT-EAN 4 d and 6 d following cell transfer. After nerve transection no gamma-IFN-positive cells were found in the distal stumps. The localization of gamma-IFN in nerve roots indicates an important role of this lymphokine in acute immune-mediated demyelination. gamma-Interferon most likely locally affects macrophage functions such as migration, major histocompatibility complex (MHC) class II antigen (Ia) expression, and production of cytotoxic molecules in nerves, and thereby contributes to myelin damage.


Autosomal dominant pure cerebellar ataxia. Neurological and genetic study.

A family with late-onset autosomal dominant pure cerebellar ataxia was studied both neurologically and genetically. Neuroimaging and electrophysiological results were in agreement with the clinical evidence showing involvement of the cerebellar system only, even many years after onset. No atrophy of inferior olives was observed by magnetic resonance imaging, while cerebellar atrophy was extremely marked. A very slow disease progression was observed in all patients. The disease can be differentiated from autosomal dominant olivo-ponto-cerebellar atrophies, and in particular from spinocerebellar ataxia type 1 mapping on chromosome 6p, which shows an early multisystemic involvement and a more rapid progression toward inability. A genetic study of the family with the 6p DNA marker D6S89 closely linked to the spinocerebellar ataxia type 1 locus was performed. Results showed significant exclusion of a linkage between the disease and the marker within a distance of 8.5% recombination, indicating that genetic heterogeneity underlies phenotypic differences.


Occipital lobe epilepsy: electroclinical manifestations, electrocorticography, cortical stimulation and outcome in 42 patients treated between 1930 and 1991. Surgery of occipital lobe epilepsy.

Our study documents the clinical and electrographic findings in 42 patients with medically refractory occipital lobe epilepsy, who underwent surgery at the Montreal Neurological Institute between 1930 and 1991, and the evolving manner in which those patients were studied by successive generations of investigators. In more than two-thirds of the patients the clinical manifestations indicated the occipital onset of the seizures. Seventy-three percent experienced visual aurae, of which elementary hallucinations were the most common and 12 also had ictal blindness. Other occipital manifestations included: contralateral eye deviation, blinking, a sensation of eye movement and nystagmoid eye movements. Intra-operative cortical stimulation elicited a habitual aura in 37% of 29 patients. Lateralizing clinical features were seen in almost two-thirds of patients: contralateral head deviation occurred in half, 59% had visual field defects contralateral to the epileptogenic area and 64% had abnormal imaging studies ipsilateral to the side of surgery. More than one-third of patients exhibited more than one seizure type, suggesting ictal spread to temporal or frontal lobe: 50% had typical temporal lobe automatisms, and 38% exhibited focal motor seizure activity. Surface electroencephalogram (EEG) recordings showed posterior temporal-occipital epileptiform discharges in 46% of patients. Only 18% had electronegative spiking limited to 01 or 02. Large epileptogenic areas were often found on intracranial recording with depth electrodes and on electrocorticography. Pre-excision electrocorticography spiking was restricted to the occipital lobe in only 13 out of 34 patients. More often spiking also involved the posterior temporal and posterior parietal regions. Twenty-three patients underwent only occipital resections; five had only temporal resections, so as to preserve the visual fields, and the remaining 14 patients had extensive resections, which included the posterior temporal or posterior parietal regions. A follow-up period of 1 to 46 yrs (mean 17 yrs) was available for 37 patients. Forty-six percent became seizure free and 21% had a significant reduction in seizure frequency. A better outcome was observed in those patients in whom there was no post-resection electrocorticographic or surface EEG epileptiform discharge, or who exhibited an occipital lobe lesion.


Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients.

The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.


Fronto-striatal cognitive deficits at different stages of Parkinson's disease.

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease.


The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.


The cortical localization of the lexicons. Positron emission tomography evidence.

Positron emission tomography was used to investigate changes in regional cerebral blood flow (rCBF) in neurologically normal subjects during word reading and word repetition. The blood flow in these conditions was compared with control conditions where subjects were presented with stimuli of comparable auditory and visual complexity to real words and said the same word on presentation of each stimulus. The control condition for word repetition (hearing spoken words presented backwards) resulted in bilateral activation of the superior temporal gyrus. Word repetition caused a significant increase in rCBF over this control condition in the left superior and middle temporal gyri. The control condition for word reading (seeing stimuli written in 'false fonts', i.e. non-existent letter-like forms) resulted in significant changes in rCBF bilaterally in the striate and extrastriate cortex. Word reading caused a significant increase in blood flow relative to this control in the posterior part of the left middle temporal gyrus. The implications of these results are discussed, and it is argued that they are consistent with localization of a lexicon for spoken word recognition in the middle part of the left superior and middle temporal gyri, and a lexicon for written word recognition in the posterior part of the left middle temporal gyrus.


Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy.

We report five patients with a stereotyped clinical syndrome characterized by fluent dysphasia with severe anomia, reduced vocabulary and prominent impairment of single-word comprehension, progressing to a stage of virtually complete dissolution of the semantic components of language. A marked reduction in the ability to generate exemplars from restricted semantic categories (e.g. animals, vehicles, etc.) was a consistent and early feature. Tests of semantic memory demonstrated a radically impoverished knowledge about a range of living and man-made items. In contrast, phonology and grammar of spoken language were largely preserved, as was comprehension of complex syntactic commands. Reading showed a pattern of surface dyslexia. Autobiographical and day-to-day (episodic) memory were relatively retained. Non-verbal memory, perceptual and visuospatial abilities were also strikingly preserved. In some cases, behavioural and personality changes may supervene; one patient developed features of the Kluver-Bucy Syndrome. Radiological investigations have shown marked focal temporal atrophy in all five patients, and functional imaging by single positron emission tomography and positron emission tomography (one case) have implicated the dominant temporal lobe in all five. In the older literature, such cases would have been subsumed under the rubric of Pick's disease. Others have been included in series with progressive aphasia. We propose the term semantic dementia, first coined by Snowden et al. (1989), to designate this clinical syndrome.


The topography of callosal reading pathways. A case-control analysis.

Lesion topography and reading ability were analysed in 17 patients with dominant posterior cerebral artery territory infarction. Patients with dominant posterior cerebral artery infarction in whom reading was unaffected served as an anatomical control group. Normal readers had lesions in the medial and ventral occipital lobe, sparing dorsal white matter pathways and the ventral temporal lobe. Global and permanent alexia occurred only with additional injury to the splenium, forceps major or white matter above the occipital horn of the lateral ventricle. These data suggest that callosal pathways mediating reading lie above the occipital horn and have little connection with the ventromedial occipital region. Patients with 'spelling dyslexia' had large lesions of the ventral temporal lobe involving cortical regions believed to participate in later stages of visual processing. These findings provide a framework for the prediction of dyslexia type and severity based on lesion topography.


Amnesia following a discrete basal forebrain lesion.

Destructive lesions of the basal forebrain are associated with memory impairment in both humans and experimental animals. The basal forebrain is thought to contribute to memory function by providing cholinergic innervation to critical memory structures such as the hippocampus and amygdala. In previously reported clinical cases of basal forebrain amnesia, multiple neuroanatomical regions have been damaged, preventing identification of the minimal critical lesion necessary to produce an amnestic syndrome. We describe a patient who developed persistent, global anterograde and retrograde amnesia following resection of a low-grade glioma. Post-surgical magnetic resonance imaging studies revealed a small discrete lesion, centred in the right diagonal band of Broca, that included the preoptic area, the anterior hypothalamus, the lamina terminalis and the paraterminal gyrus. The septal nuclei and the cell bodies of the nucleus basalis of Meynert appeared to have been spared, as were other structures in the medial temporal lobe and diencephalon. Our case provides critical support for the independent contribution of the basal forebrain, in particular the diagonal band nuclei, in memory function. We propose that our patient's amnesia resulted from disconnection of pathways between the diagonal band nuclei and the hippocampal region, depriving the hippocampus of cholinergic innervation.


Impairments of movement initiation and execution in unilateral neglect. Directional hypokinesia and bradykinesia.

Patients with unilateral neglect may exhibit slowness in the initiation of contralesionally directed movements in peripersonal space (directional hypokinesia). The present study used a sequential movement task to characterize any such impairment in a group of 24 patients with right hemisphere lesions, 18 of whom had left neglect. A further five patients with left hemisphere lesions, one of whom had right neglect, were also tested. We measured movement initiation and execution times for leftward and rightward movements in either hemispace and across the body midline. Most left neglect patients, particularly those with lesions involving posterior cortex, showed directional hypokinesia. Left neglect patients with anterior and/or subcortical lesions also showed directional bradykinesia, i.e. a slowing in the execution phase of contralesionally directed movements. This impairment occurred regardless of the spatial location of the apparatus and was exacerbated as patients moved closer to their neglected side. The patient with right neglect showed directional hypokinesia but not directional bradykinesia. Right hemisphere and left hemisphere lesion patients without neglect performed in a manner comparable to controls, who did not exhibit directional hypokinesia or directional bradykinesia. These results suggest that directional hypokinesia is associated with both left hemisphere and right hemisphere damage, but only in the context of unilateral neglect. Moreover, the site of hemispheric lesion may determine the temporal characteristics of movement impairments in neglect. Damage to posterior cortex produces deficits in detecting contralesional targets and initiating movements toward them, while damage to anterior or subcortical structures may disrupt the internal representation of an intended trajectory.


Stimulus-sensitive myoclonus in akinetic-rigid syndromes.

The cutaneous reflexes of upper limb muscles were studied in five patients with Parkinson's disease and 10 patients with stimulus-sensitive myoclonus associated with akinetic-rigid syndromes. The middle finger was stimulated with ring electrodes and rectified electromyographs were averaged from seven upper limb muscles and orbicularis oculi. Responses from subjects with Parkinson's disease without stimulus-sensitive myoclonus were similar to those of normal subjects. The responses from patients with stimulus-sensitive myoclonus associated with Parkinson's disease or multiple system atrophy had the normal pattern except that a long latency facilitation, which is present in normal subjects and known as E2, was greatly exaggerated. Patients with stimulus-sensitive myoclonus associated with cortical-basal ganglionic degeneration had a completely different pattern of responses. There was synchronous activation of all recorded upper limb muscles with latencies substantially shorter than those of the long latency facilitation (E2) in normal subjects. Cutaneous reflex testing may therefore be useful in the differentiation of akinetic-rigid syndromes.


Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease.

Fazio-Londe disease is a label sometimes applied to a degenerative disease of the motor neurons characterized by progressive bulbar paralysis in children. It is very rare with only 22 case reports describing 24 children including four sibling pairs. In two reports mothers and sons were affected. The neuropathology is described in only four cases. Previous authors have recognized that the condition is very heterogeneous. The clinical features of five children with this type of progressive bulbar paralysis, diagnosed at this hospital between 1969 and 1989, are reviewed, and in two cases neuropathological findings are detailed. Based on this experience, suggested criteria for diagnosis include clinical features of a pure motor neuronopathy affecting the bulbar nuclei, exclusion of other causes of progressive bulbar paralysis and positive support for the diagnosis from electromyography and/or pathological examination. A review of the literature, combined with the present series, suggests that there are at least three distinct subtypes: a very rare autosomal dominant form (as described by Fazio) and two variants with probable autosomal recessive inheritance either with early onset of respiratory symptoms and rapid progression to death or later onset, less prominent respiratory symptoms and protracted clinical course. There is strong concordance for each clinical pattern within families.


Acquired monocular elevation paresis. An asymmetric upgaze palsy.

Five patients with acquired monocular elevation paresis were investigated using direct current electroculography. With recovery, upward saccade velocities significantly increased in both eyes in all patients. The gain of upward-following eye movements significantly increased in the paretic eye of all patients and in the opposite eye of four patients. These findings are interpreted in terms of an asymmetric upgaze palsy which clinically presented as monocular elevation paresis in the more severely affected eye. A brainstem lesion contralateral to monocular elevation paresis was suggested in four patients by contralateral Horner's syndrome and contralateral abduction paresis, each in one patient, and contralateral ptosis in two patients. In only one patient, computerized tomography and magnetic resonance imaging substantiated a contralateral meso-diencephalic lesion.


The mysterious relocation of the bundle of Türck.

The name bundle of Türck has become synonymous with the temporopontine tract. As details concerning this pathway have been confusing and incomplete we reviewed the papers of Ludwig Türck (1810-1868) to determine what in fact he originally described. Türck's pioneering degeneration studies provided great detail concerning the corticospinal tracts. Charcot recognized his contributions and used the eponym 'bundle of Türck' to denote the anterior corticospinal tract. Türck did not observe projections from the temporal lobe to the basis pontis, nor did he describe a temporopontine tract located at the most lateral aspect of the cerebral peduncle. The papers of Meynert, Flechsig and others reveal the origins of the current incorrect use of the eponym.


The relationship between electrophysiological findings, upper limb growth and histological features of median and ulnar nerves in man.

In 19 median and 10 ulnar nerves of 28 healthy young volunteers, the maximum orthodromic sensory conduction velocity was studied along one or two fingers (the third and/or the fifth), the palm, and the forearm. In five 20 to 32-yr-old males and in a newborn male, post-mortem samples of either the median or the ulnar nerve were obtained from the finger (either the third or the fifth), the palm, the wrist and the forearm in order to study the size distribution of external fibre and axon diameters, and the fibre internodal length. In 2374 infants, children and adolescents, the height, length of both the third and the fifth finger, length of the palm, and length of the forearm were measured. The results showed (i) a significantly slower conduction velocity along the fingers; (ii) a significantly shorter internodal length without remarkable fibre diameter changes in the same nerve segments; (iii) a significantly smaller elongation of these body parts; (iv) a significant correlation between these data. In conclusion, internodal length seems to play an important role in governing conduction velocity of myelinated peripheral nerve fibres.


Stimulation of corticospinal pathways at the level of the pyramidal decussation in neurological disorders.

A newly developed technique of brainstem stimulation was applied in 14 normal subjects and 23 patients with various neurological disorders. The electromyographic (EMG) responses of limb muscles following cortical, brainstem and cervical stimulation were recorded. The cortical-brainstem conduction time and brainstem-cervical conduction time were then calculated from the difference in latency between the two sites of stimulation. From the regression lines of the relationship between the normal conduction times in the first dorsal interosseous muscle and the length of the descending tracts, the site of activation by brainstem stimulation was estimated to lie near the cervical-medullary junction. The most distal lesion causing prolongation of cortical-brainstem conduction time was a small cerebral infarction in the lower pons. Herniation of the third cervical spinal disc was the most rostral lesion resulting in delayed brainstem-cervical conduction time and normal cortical-brainstem conduction time. These observations suggest that activation occurs at the level of the cervical-medullary junction where the pyramidal decussation lies. The conduction velocities of the activated tracts estimated from the regression lines for normal individuals were 57-92 m/s. In patients with supratentorial lesions, the threshold for brainstem stimulation was abnormally high. The abnormal findings in this test were correlated significantly with the clinical pyramidal signs. This suggests that the EMG responses elicited by brainstem stimulation are mediated mainly by the corticospinal tract. We conclude that the brainstem stimulation technique would be clinically useful for localization of lesions in the corticospinal tract; the primary lesion can be localized whether above or below the pyramidal decussation.


Progressive impairment of Schwann cell proliferation in vitro in murine globoid cell leukodystrophy (twitcher).

In an attempt to elucidate possible functional derangement in Schwann cells in globoid cell leukodystrophy (GLD), we investigated the proliferative capacity in vitro of Schwann cells from the twitcher (twi/twi), a murine model of human GLD, with thymidine autoradiography and cell counts. Regardless of genotype, Schwann cell numbers increased faster and initial thymidine incorporation was higher in suckling than in adult mice. Compared with cells from heterozygous (+/twi) or normal (+/+) mice, however, proliferative capacity of Schwann cells from twi/twi was depressed in both sucklings and adults. Reflecting in vivo activation secondary to demyelination, the number of labeled Schwann cells was transiently higher during the first 24 h in adult twi/twi cultures but the rate of proliferation declined thereafter and remained low during an 8 day period in culture. Our study demonstrates that proliferative capacity of twi/twi Schwann cells was impaired in vitro, possibly as a consequence of metabolic perturbation by a deficiency of galactosylceramidase.


Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T.

The envelope protein of the human immunodeficiency virus (gp120) causes neuronal death in developing murine hippocampal cultures or rat retinal ganglion cells. In HIV-infected individuals, gp120 released from HIV-infected macrophages or other cells in the brain has been proposed as the etiology for the pathophysiology of AIDS central nervous system (CNS) disease by diffusing to act at a distance to cause damage and/or death to neighboring neurons. In this study, 28 cerebrospinal fluid (CSF) samples from HIV-infected individuals (79% were WR stage 1 and 2) and neurological disease controls were tested, blind to the investigator, for the presence of in vitro neuronal killing activity. Neurotoxic activity was detected with peak effects at a 1:10(5) dilution in CSF from 9/18 HIV-infected individuals and 1/10 neurological disease controls. Thus half of CSF from early stages of HIV disease are characterized by the presence of neurotoxic activity which is not present in control CSF (Fischers exact test, P < 0.05). The neuronal toxicity by patient CSF could be prevented by peptide T (1 nM). A monoclonal antibody to mouse CD4, RL.172, also attenuated or prevented CSF-induced neuronal killing in all four CSF samples tested. In addition, an antiserum to peptide T previously shown to bind gp120 and neutralize both infectively and direct gp120 neurotoxicity, neutralized the CSF factor. gp120, or a modified small fragment, is suggested to be the responsible toxic molecular entity. These results may be relevant to the pathophysiology of HIV-related CNS disease and the mechanism by which peptide T causes improvements.


A cholinergic input to the substantia nigra pars compacta increases striatal dopamine metabolism measured by in vivo voltammetry.

3,4-Dihydroxyphenylacetic acid (DOPAC) and ascorbic acid (AA) were measured by differential pulse voltammetry in the neostriatum of anesthetized rats. Physostigmine (2.3 nmol) applied into the substantia nigra pars compacta (SNc), increased DOPAC concentration in the ipsilateral neostriatum, but did not modify AA levels. The largest increase of striatal DOPAC (37 +/- 8% above basal) was observed when physostigmine was applied at less than 0.5 mm from SNc, and decreased with increasing distance of the injection site from the pars compacta region. Chemical stimulation of the pedunculopontine tegmental nucleus (PPN) with kainic acid (2.3 nmol) increased both DOPAC and AA concentration in the ipsilateral neostriatum. Pretreatment with the muscarinic antagonist scopolamine (5 mg/kg, i.p.) inhibited the increase of striatal DOPAC from 20 to 70 min after kainic acid injection into the PPN, whereas the increase of AA was reduced from 90 to 160 min. By contrast, the nicotinic antagonist mecamylamine (4 mg/kg, i.p.) did not inhibit neither DOPAC nor AA increase elicited by the chemical stimulation of PPN. These results support the existence of cholinergic neurotransmission within the SNc that increases the firing rate of nigrostriatal dopaminergic neurons, enhancing dopamine turnover in neostriatum without changes in AA release. They also suggest that the PPN could be the origin of cholinergic afferents to the SNc that modulate the activity of dopaminergic neurons, through activation of muscarinic cholinergic receptors. Finally, the activation of a multisynaptic loop involving a cholinergic pathway which modulates the activity of the glutamatergic corticostriatal neurons is postulated to explain the increase of AA in neostriatum observed after PPN stimulation.


Comparative effects of electroconvulsive shock and haloperidol on in vivo tyrosine hydroxylation and tetrahydrobiopterin in the brain of rats with 6-hydroxydopamine lesions.

We have evaluated the effects of electroconvulsive shock (ECS) and haloperidol treatment on the in vivo tyrosine hydroxylation rate and the tetrahydrobiopterin levels in the nigrostriatal system of 6-OHDA-lesioned rats. The rate of DOPA accumulation was significantly decreased by 96% in the ipsilateral striatum and by 50% in substantia nigra of the 6-OHDA-lesioned rats compared to the control activity of contralateral non-lesioned striatum and substantia nigra. The loss of total biopterin was found to be 75% and 50% in the ipsilateral striatum and substantia nigra, respectively. Following administration of haloperidol, the rate of DOPA accumulation increased significantly in the striatum and substantia nigra on the lesioned side compared to that in the vehicle treatment group. Application of ECS also significantly increased the rate of DOPA accumulation in the ipsilateral striatum and substantia nigra compared to that obtained in the non-shocked rats. The biopterin levels in the nigrostriatal system of 6-OHDA-lesioned were elevated significantly in the striatum after haloperidol treatment; in contrast the biopterin levels were unchanged in response to ECS. Our results show that both haloperidol and ECS significantly enhanced the rate of in vivo tyrosine hydroxylation in the striatum and substantia nigra of rats with greater than 90% lesions. These results suggest that the nigrostriatal system, although up-regulated following 6-OHDA lesions, still maintains the potential for further up-regulation of dopaminergic function in response to haloperidol and ECS treatment.


Anatomical and electrotonic coupling in developing genioglossal motoneurons of the rat.

Dye-, tracer- and electrotonic coupling were studied independently in genioglossal (GG) motoneurons using intracellular recordings in in vitro brainstem slices from rats postnatal ages 1-30 days. The subpopulation of GG motoneurons were retrogradely labeled after an injection of dextran-rhodamine into the posterior tongue. Dye-coupling was studied with Lucifer yellow injected into 55 motoneurons and tracer-coupling with neurobiotin injected into 89 presumptive GG motoneurons. Of the motoneurons injected with Lucifer yellow, only 6 of 41 cells (16.2%) exhibited dye-coupling; all occurred in animals less than 9 days old. In all but one instance, dye-coupling was restricted to only one other cell. No evidence of dye-coupling was found in the 14 cells injected in animals older than 8 days. Tracer-coupling (neurobiotin) was demonstrated in 12 of 30 cells (40%) from animals 1-2 days old and in 6 of 21 cells (28.6%) from animals 3-8 days old. Of the remaining 38 cells from animals 10 days of age and older, only one cell was found to be tracer-coupled. Cells injected with neurobiotin were coupled to an average of two other cells. Electrotonic coupling, as demonstrated with a short latency depolarization (SLD) in response to stimulation of hypoglossal axons, was found in developing GG motoneurons. These SLDs were revealed in 17 of 40 GG motoneurons (42.5%) examined in 1-8-day-old animals. There were no SLDs recorded in the 10 cells examined from animals of 10 days and older. The significance of coupling relative to patency of the newborn upper airways is discussed.


A peptidergic circuit for reproductive behavior.

A projection from the medial amygdaloid nucleus to the hippocampus and septum probably uses vasopressin as a transmitter. The nucleus synthesizes vasopressin and activation of the nucleus has a hippocampal effect that is completely blocked by a vasopressin antagonist. The afferent and efferent projections of this peptidergic nucleus suggest a possible role for the system in sexual behavior. Stimulation of the nucleus inhibits the output of the hippocampus in both genders and reorganizes behavior for a period of 15-20 min. In males, the effect of peptidergic activation is to produce a behavior that resembles the post-ejaculatory interval in coitus. This state is characterized by an EEG that resembles slow-wave sleep and by ultrasonic vocalizations at a characteristic frequency of 22 kHz. Castration in either gender causes depletion of the peptide from the target fields and eliminates the peptidergic signal in the hippocampus after about 15 weeks. The effects of castration in males can be reversed by testosterone replacement. The fluctuation of estrogen levels in rat plasma during the estrus cycle happens too quickly to impact the peptidergic system, and thus there is no significant change in the strength of the peptidergic signal among the proestrus, estrus, metestrus and diestrus stages. This fact permits study of the physiology of the system without concern for stage of estrus but does not permit conclusions regarding its function in females.


Fiber composition of the human corpus callosum.

The densities of fibers of different sizes were calculated in ten regions of the corpus callosum of twenty human brains (ten females, ten males). Light microscopic examination revealed a consistent pattern of regional differentiation of fiber types in the corpus callosum. Thin fibers are most dense in the anterior corpus callosum (genu), and decrease in density posteriorly towards the posterior midbody, where they reach a minimum. Towards the posterior corpus callosum (splenium), the density of thin fibers increases again, but in the posterior pole of the callosum the density decreases locally. Large-diameter fibers show a pattern complementary to that of thin fibers, having a peak of density in the posterior midbody and a local increase of density in the posterior pole of the corpus callosum. Across subjects, the overall density of callosal fibers had no significant correlation with callosal area and an increased callosal area indicated an increased total number of fibers crossing through. Considering different fiber sizes, this was only true for small diameter fibers, whose large majority is believed to interconnect association cortex. No sex differences in fiber composition of the corpus callosum were found.


Individual differences in brain asymmetries and fiber composition in the human corpus callosum.

There have been several recent reports concerning individual differences in the gross morphometry of the human corpus callosum. However, no studies exist on individual differences in the fiber composition of the corpus callosum. Here we report for the first time the relation of fiber composition in specific callosal segments (as seen in light microscopy) to anatomical asymmetries in language-gifted cortex, as a function of sex. We found a significant negative correlation between Sylvian fissure asymmetries and the total numbers of fibers in the isthmus of males, and in the anterior splenium of females. In addition, a population of relatively large fibers (between 1 micron and 3 microns in diameter) in the isthmus showed a strong negative correlation with perisylvian asymmetries only in males. These findings suggest a sex-dependent, pathway-specific decrease in interhemispheric connectivity with increasing lateralization.


Factors regulating the magnitude of long-term potentiation induced by theta pattern stimulation.

Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long-term potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine A1 receptors, was used to enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP. These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning are also considered.


Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity.

NMDA receptor activation leads to elevated Ca2+ in cultured rat cortical and retinal ganglion cell neurons. If excessive, this Ca2+ response is associated with delayed neurotoxicity. We used dantrolene and ionomycin to test if the Ca2+ response to NMDA was due to mobilization of intracellular Ca2+ stores rather than merely to Ca2+ influx. In the presence of EGTA, ionomycin resulted in release and subsequent depletion of intracellular Ca2+ stores. Henceforth, despite normal extracellular Ca2+, NMDA elicited only about half of its former Ca2+ response. Similarly, when dantrolene was used to block Ca2+ release from intracellular stores, we observed > 50% smaller NMDA-evoked Ca2+ responses. These results quite surprisingly indicate that at least half the Ca2+ response to NMDA is due to release of intracellular Ca2+, a process triggered by influx of extracellular Ca2+. Dantrolene also protected neurons from NMDA receptor-mediated neurotoxicity. Release of intracellular Ca2+ may therefore be a necessary step in the cascade leading to neuronal damage induced by excessive NMDA receptor stimulation and may be amenable to pharmacological intervention.


Cerebrovascular nerve fibers immunoreactive for tryptophan-5-hydroxylase in the rat: distribution, putative origin and comparison with sympathetic noradrenergic nerves.

The distribution of serotonergic nerves in major basal and isolated small pial arteries (diameter > or = 50 microns) was investigated immunohistochemically using an antibody directed against tryptophan-5-hydroxylase (TPOH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine (5-HT or serotonin), and compared to that of the noradrenergic system labeled for the selective noradrenaline (NA) synthesizing enzyme, dopamine-beta-hydroxylase (DBH). In addition, the possible peripheral and/or central origins of the cerebrovascular serotonergic (TPOH-positive) nerve fibers were examined. Strongly labeled TPOH-immunoreactive (TPOH-I) fiber bundles were observed in major basal arteries and gave rise to small varicose fibers organized in a meshwork pattern. The highest density of TPOH-I fibers was found in the middle cerebral artery followed by the anterior cerebral and the anterior communicating arteries, with a moderate to low density in the internal carotid and the vertebro-basilar trunk. Of the isolated pial arteries, only the larger ones (diameter > 75 microns) were significantly endowed with TPOH-I varicose fibers. However, free floating TPOH-I nerves were observed coursing through the pia-arachnoid membranes and reaching small pial vessels. In contrast, DBH-I nerve fibers were fine and were visualized primarily as numerous varicosities distributed in a circumferential manner around the vessel wall. A very high density of DBH-I varicosities was seen in the rostral part of the circle of Willis, with the internal carotid being the most richly supplied followed by the anterior cerebral and the anterior communicating arteries; comparatively, the middle cerebral artery was moderately innervated. The differences in distribution pattern and density between TPOH-I and DBH-I cerebrovascular fibers clearly suggest that these two innervation systems are not exactly superimposable. Superior cervical ganglionectomy caused an almost complete disappearance of TPOH-I nerves in all vascular segments, with some residual fibers in selected vessels. Lesion of the central serotonergic component with the neurotoxin 5,7-dihydroxytryptamine had virtually no effect on the TPOH-I fibers in the major basal and isolated pial arteries. These results strongly suggest that the serotonergic innervation of major cerebral as well as pial arteries has a prominent peripheral origin closely related to the sympathetic system. Processing of superior cervical ganglion slices for TPOH immunocytochemistry, however, failed to unequivocally detect TPOH-I neurons.


A new type of Ca2+ channel blocker, NC-1100, inhibits the low- and high-threshold Ca2+ currents in the rat CNS neurons.

The effect of a new type of organic Ca2+ channel blocker, NC-1100 [(+/-)-1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)etha nol dihydrochloride], on both low- and high-threshold Ca2+ currents was studied in the whole-cell mode of the pyramidal neurons freshly dissociated from rat hippocampal CA1 region under voltage-clamp condition. The NC-1100 reversibly reduced the high-threshold Ca2+ current (HVA ICa) in a concentration-dependent manner without affecting the current-voltage relationship. The values of half-inhibition (IC50) were 1.3 x 10(-5) and 9.1 x 10(-6) M in external solution containing 10 and 2.5 mM Ca2+, respectively. The NC-1100 also decreased the low-threshold Ca2+ current (LVA ICa) in a concentration-dependent manner. The inhibitory potency was augmented by increasing the stimulation frequency and/or decreasing the extracellular Ca2+ concentration to a physiological range (2.5 mM). The IC50 value decreased to 7.7 x 10(-7) M in external solution containing 2.5 mM Ca2+ at a stimulation frequency of 1 Hz. The NC-1100 delayed the reactivation of LVA Ca2+ channel and enhanced voltage-dependently the steady-state inactivation, suggesting that this drug bound not only the resting LVA Ca2+ channel but also the inactivated one.


Ca(2+)-binding proteins in rat synaptic fractions surveyed by the 45Ca2+ overlay method.

Ca(2+)-binding proteins in the synaptic and subsynaptic fractions (P2, synaptosome, synaptic plasma membrane, and postsynaptic density [PSD]-enriched fractions) and soluble fraction of rat brain were surveyed by a 45Ca2+ overlay method. The PSD-enriched fraction from cerebral cortex contained two major Ca(2+)-binding proteins (55,000 M(r) and 19,000 M(r)) and a distinct group (in 140,000 M(r) region), and two minor ones (66,000 M(r) and 16,000 M(r)); and the fraction from cerebellum contained two (55,000 M(r) and 19,000 M(r)). The proteins with 55,000 M(r) and 19,000 M(r) were identified as tubulin and calmodulin, respectively, and present in all the fractions investigated. The Ca(2+)-binding proteins of 140,000 M(r) region were found only in the PSD-enriched fraction isolated from cerebral cortex: neither the PSD-enriched fraction isolated from cerebellum nor other subcellular fractions prepared from cerebral cortex and cerebellum contained the proteins. The 140,000 M(r) Ca(2+)-binding proteins were the substrates for the Ca2+/calmodulin-dependent protein kinase II associated with PSD, and no change in the Ca(2+)-binding was detected by the 45Ca2+ overlay method after phosphorylation of the proteins by the protein kinase. The 16,000 M(r) Ca(2+)-binding protein might be the beta-subunit of calcineurin. Calretinin and calbindin-D28k were also detected as Ca(2+)-binding proteins in the soluble fractions of both cerebral cortex and cerebellum.


Spinal dopaminergic system of the rat: light and electron microscopic study using an antiserum against dopamine, with particular emphasis on synaptic incidence.

The mapping of the spinal dopaminergic innervation has been performed in the adult rat using an anti-dopamine antiserum. Immunoreactive fibers were detected with the light microscope in the dorsal horn (mainly in laminae III-IV), in the intermediolateral cell column (IML), in the peri-ependymal region and in the ventral horn. The ultrastructural analysis of dopaminergic innervation showed mainly axodendritic contacts and fewer axosomatic ones. In the ventral horn and the IML, the pattern of dopaminergic innervation exhibited a majority of classical synapses. In the dorsal horn, dopaminergic innervation was partly non-synaptic (at cervical level), whereas numerous axodendritic synapses were observed at thoraco-lumbar level. Previous studies described the non-synaptic organization of serotonergic and noradrenergic projections in the dorsal horn. It is thus hypothesized that the monoaminergic systems, involved in pain modulation within the dorsal horn, act partly through volume transmission. In contrast, these systems would modulate the motor and autonomic functions through classical synapses.


Brain vasculature and mitochondrial responses to ischemia in gerbils. I. Basic anatomical patterns and biochemical correlates.

A unique blood supply to the brain, the 'Circle of Willis' (COW), exists in all mammals except for the Mongolian gerbil (Meriones unguiculatus). This system is capable of compensating for a decrease in blood supply in one of the four arteries, which may occur during pathological conditions. The posterior connection between the basilar artery and the carotid artery system have been found to be missing in most gerbils. Furthermore, in some of the animals, the anterior communication was not complete, thus leading to partial ischemia following unilateral carotid artery occlusion. Due to those peculiar characteristics, the Mongolian gerbil today has become a widespread animal model for cerebral ischemia studies. M. unguiculatus has been used in most of the studies while the level of ischemia has been evaluated by the development of neurological symptoms created by the occlusion of the carotid arteries. In the present study we investigated the vasculature structure of the commonly used gerbil, M. unguiculatus (MU-TF) and compared it to the vasculature of the Israeli gerbil, Meriones tristrami as well as to that of the Albino rat. We determined the correlation between the anatomical pattern and the biochemical responses during partial or complete ischemia and anoxia by monitoring the oxidation-reduction state of the intramitochondrial NADH using an in vivo surface fluorescence technique. The corrected fluorescence signal was found to be inversely correlated with oxygen availability and could thus be used as an indicator for the level of ischemia developed after carotid artery occlusion. This is the first time that the brain vasculature of two lines of M. tristrami (MT-HU, MT-BD) has been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain vasculature and mitochondrial responses to ischemia in gerbils. II. Strain differences and statistical evaluation.

The correlation between the anatomy of brain vasculature and the metabolic responses to ischemia was studied in two strains of the Mongolian gerbil as compared to the albino rat. Gerbils belonging to the Meriones unguiculatus obtained from Tumblebrook Farms and from the NY Institute for Basic Research were compared to two lines of the Meriones tristrami obtained from two different breeders in Israel. In all groups of gerbils and in the albino rats, a significant correlation was found between the anatomical patterns of the Circle of Willis and the metabolic responses to ischemia as evaluated by NADH redox state measurements, namely, that with a complete anterior anatomical Circle of Willis the metabolic response to unilateral occlusion was minimal. In the anterior part of the Circle of Willis the various groups of gerbils exhibited the entire range of ischemia levels, from 0-100%, depending upon the anatomical structure of the arteries. In M. tristrami, the anterior communications between the two hemispheres were very well developed as compared to the various degrees of connection found in the different individuals of M. unguiculatus. This anatomical pattern corresponds well to the metabolic response recorded under unilateral and bilateral occlusion. The best connection in the posterior part, was found in M. tristrami. This was less frequent (10-20% of the gerbils) in M. unguiculatus. A clear correlation was found between the size of the posterior communicating artery and the changes in NADH redox state measured during bilateral carotid artery ligation. The variation between gerbils of the same litter was significantly smaller than that of the general population of the same strain.(ABSTRACT TRUNCATED AT 250 WORDS)


The relation between light-induced discharge in the suprachiasmatic nucleus and phase shifts of hamster circadian rhythms.

The role of neurophysiological activation of suprachiasmatic nucleus (SCN) cells in phase shifting the circadian pacemaker of the hamster was investigated in a combined behavioural and electrophysiological study. An electrophysiological study examined the relation between the pattern of light presentation and the induced discharge rate in the SCN. Behavioural experiments examined the relation between the pattern of light presentation and the magnitude of phase shift induced. The combination of these results provides an indirect assay of the relations between induced neural discharge in the SCN and phase shifts of the circadian activity rhythm. The data indicate that the magnitude of phase shifts is monotonically, but not linearly, related to photically induced changes in discharge rate.


Effects of nerve growth factor and basic fibroblast growth factor on survival of cultured septal cholinergic neurons from adult rats.

We have established a primary culture technique for neuronal cells from rat basal forebrain from postnatal day 58 (P58) to study the effects of neurotrophic factors on the neurons. The survival of acetylcholinesterase (AChE)-positive neurons of 2-week-old rat septum has already been reported to be strongly supported by nerve growth factor (NGF) in culture. In this culture study of neurons from adult rat brains, the survival of AChE-positive neurons from P58 rat septum was slightly improved by NGF, although low affinity NGF receptor expression was also observed on cultured P58 rat septum neurons as well as on those from 2-week-old rats. The addition of basic fibroblast growth factor (bFGF) improved the survival of AChE-positive neurons cultured from P58 rat septum, but did not promote the survival of neurons from P12 rat septum. These results suggest that NGF changes to a maintenance factor in adult rat brain from a survival factor in postnatal 2-week-old rats. The survival of cholinergic neurons in culture of adult rat septum might be supported by factor(s) other than NGF, such as bFGF.


Characterization of the release of Met-enkephalin from isolated nerve terminals: release kinetics and cation-dependence.

The release of the neuropeptide Met-enkephalin (Met-ENK) from isolated nerve terminals (synaptosomes) of the rat forebrain was characterized with respect to the subcellular distribution, the release upon addition of various stimulatory agents, the release kinetics, the cation-dependence of release and the relationship between Met-ENK release and elevations of the intraterminal free Ca(2+)-concentration ([Ca]i). A highly specific radioimmunoassay was developed for determination of Met-ENK (H-Tyr-Gly-Gly-Phe-Met-OH). Truncated and elongated forms of Met-ENK, Leu-enkephalin, beta-endorphin and dynorphin displayed negligible cross-reactivity. Met-ENK-like immunoreactivity (Met-ENK-LI) is enriched in the purified synaptosomal fraction of rat forebrain homogenates and is released in a strictly Ca(2+)-dependent manner upon chemical depolarization or stimulation with the Ca2+ ionophore, ionomycin. A correlation exists between the release of Met-ENK-LI and the elevations of [Ca]i. Barium ions are able to replace Ca2+ in triggering Met-ENK-LI release. The release of Met-ENK-LI is initiated within 20 s after depolarization and is terminated after 3-5 min, although depolarization and [Ca]i elevation are maintained. At this time, > 90% of the initial Met-ENK-LI is still present inside the synaptosomes. Repolarization and renewed stimulation again evokes Ca(2+)-dependent release of this retained Met-ENK-LI. It is concluded that Met-ENK release from isolated nerve terminals is exocytotic, and that exocytosis is terminated by a regulatory mechanism in synaptosomes after 3-5 min of depolarization, a process which can be reversed by repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of aging on muscarinic receptor/G-protein coupling in the rat hippocampus and striatum.

In the striatum and hippocampus, there is a loss of sensitivity to muscarinic agonists with age which has been traced to events early in the signal transduction pathway. Our laboratory has therefore focussed on investigations at this level. The current experiments investigate the effects of age on G-protein/receptor interactions by using competitive binding assays to measure the ability of GppNHp to decrease the proportion of receptors bound to G-proteins in the absence and the presence of added Mg2+. L-[3H]Quinuclidinyl benzilate was used as a nonselective ligand and [3H]pirenzepine as an M1 selective ligand. We find that: (1) muscarinic receptors and G-proteins in the striatum appear to become loosely coupled with age, with no change in Mg2+ sensitivity. (2) M1-receptor/G-protein complexes in the hippocampus display increased sensitivity to the presence of Mg2+ with age, with those from old but not young tissue requiring added Mg2+ in order to uncouple. This effect, however, may not be M1 specific.


Perinatal cocaine exposure and functional brainstem development in the rat.

Rat pups exposed to cocaine via maternal intromission throughout gestation and lactation displayed significantly prolonged auditory brainstem response component latencies and interwave intervals. Longitudinal analysis revealed that this effect was most pronounced on the 22nd postnatal day. Increasing the rate of stimulation further impaired neurosensory transmission in the caudal auditory pathway. These results indicate that both axonal and synaptic events may be affected to some degree and the timing (age) of optimum cocaine influence suggests that delayed myelination may be involved. The corresponding retardation in general development of the cocaine exposed pups further implicates maternal, fetal and postnatal utilization of nutritional resources as the basis for this outcome.


Differential patterns of arborization of striatal and subthalamic fibers in the two pallidal segments in primates.

Double-anterograde tract-tracing experiments in the squirrel monkey (Saimiri sciureus) reveal that fibers from the striatum and the subthalamic nucleus converge onto the same neurons in both the external (GPe) and internal (GPi) segments of the globus pallidus. However, these two pallidal afferents arborize according to a different pattern in GPe and GPi. Whereas the striatal fibers closely entwined the distal dendrites of pallidal neurons in a similar fashion in both pallidal segments, the subthalamic fibers display a tight pericellular arrangement that is much more obvious in GPi than in GPe. This perisomatic arborization is similar to the pericellular contacts made by the GPe fibers terminating on GPi neurons. Such a resemblance suggests that these two types of afferents exert an opposite effect upon the cell body and proximal dendrites of GPi neurons. It also raises the possibility for striatal neurons to influence the same GPi neuron by acting directly on its distal dendrites and indirectly on its cell body via a relay in GPe.


The uremic guanidino compound guanidinosuccinic acid induces behavioral convulsions and concomitant epileptiform electrocorticographic discharges in mice.

As yet, the in vivo epileptogenic properties of guanidinosuccinic acid (GSA) remained highly conjectural, still requiring the demonstration of GSA-induced behavioral convulsions accompanied by epileptiform electrographic discharges. Therefore, Swiss mice were injected intraperitoneally (i.p.) with increasing doses of GSA. Full-blown clonic or clonic-tonic convulsions appeared in a dose-dependent manner, with a median latency of about 25 min. CD50 (convulsive dose of the drug in 50% of the animals), the LD50 (lethal dose in 50%), and their 95% confidence limits for GSA suspensions in i.p. administration were 363 (287-458) mg/kg and 579 (445-756) mg/kg, respectively. In addition, four-channel electrocorticographic (ECoG) recordings were made in freely moving mice following the injection of 700 mg/kg (CD97). Epileptiform ECoG discharges coincided with the behavioral manifestation of the GSA-induced convulsions starting with initial decrease in amplitude, occasional spike-waves (10-20 min after injection), eventually leading to sustained spiking and spike-wave activity (30-50 min after injection). Clonic convulsions induced by a CD97 dose of GSA were only moderately attenuated by high doses of i.p. phenobarbital (20, 40 and 80 mg/kg), while tonic extension and lethal effects were dose-dependently blocked. A dose of 1000 mg/kg (CD97 for tonic extension) induced tonic extension in 100% of the animals, following treatment with 20 mg/kg of phenytoin none of the animals displayed tonic extension, and following 10 mg/kg only 30% of the animals displayed tonic extension, while the occurrence of clonic convulsions was not significantly attenuated.


Striatal subregions are differentially vulnerable to the neurotoxic effects of methamphetamine.

Methamphetamine (m-AMPH) or saline was repeatedly administered to rats. One week later, the caudate-putamen of the m-AMPH-treated rats revealed a decrease in both [3H]mazindol-labeled dopamine uptake sites and tissue dopamine content. Moreover, the resulting pattern of decline in these measures was regionally heterogeneous. The ventral caudate-putamen displayed the greatest decrease in both [3H]mazindol binding and dopamine content while the neighboring nucleus accumbens and the dorsal caudate-putamen remained relatively intact. These results indicate a regional difference in the susceptibility of striatal dopaminergic terminals to the neurotoxic effects of methamphetamine.


Is the vasoactive intestinal peptide-like immunoreactivity in the rat pineal gland present in fibers originating in the superior cervical ganglion?

Serotonin N-acetyltransferase is regulated in the rat pineal gland by the gland's innervation from the superior cervical ganglion. Norepinephrine has been viewed as the sole transmitter involved in this trans-synaptic regulation; however, a possible role for vasoactive intestinal peptide (VIP) has recently emerged. VIP-like immunoreactivity was extracted from rat pineal glands and shown to co-elute on reverse-phase liquid chromatography with authentic VIP. The level of VIP-like immunoreactivity in the gland was unaffected by prior sympathetic denervation, though its level of neuropeptide Y-like immunoreactivity decreased by 85%. The results indicate that VIP and norepinephrine are not colocalized in sympathetic neurons in the pineal gland and raise questions as to the physiological role of VIP in regulation of pineal function in vivo.


The locus coeruleus and memory: a study of chronic alcoholics with and without the memory impairment of Korsakoff's psychosis.

The loss of noradrenergic locus coeruleus neurons has been identified as the possible critical lesion inducing amnesia in alcoholic patients with the Wernicke-Korsakoff syndrome. The present study aims to test this hypothesis by quantifying the number of pigmented locus coeruleus neurons in 4 alcoholics with the Wernicke-Korsakoff syndrome, 5 alcoholics with Wernicke's encephalopathy alone but no amnesia, and 1 alcoholic and 5 age-matched controls with no neurological disorders. Apart from an increased vascularity in the locus coeruleus of alcoholics, no significant differences in the number, morphology or distribution of pigmented locus coeruleus neurons was noted between any of the groups analysed. There was a significant correlation between the number of locus coeruleus neurons and brain weight. These data demonstrate that neither alcohol neurotoxicity nor thiamine deficiency result in a reduction in the number of pigmented cells in the locus coeruleus and refute the hypothesis that locus coeruleus cell loss is critical for the amnesia in the Wernicke-Korsakoff syndrome.


Circadian and developmental regulation of Oct-2 gene expression in the suprachiasmatic nuclei.

Oct-2 is a transcriptional activating factor that is expressed in the suprachiasmatic nuclei (SCN), the site of a biological clock. We examined in rats whether Oct-2 gene expression is regulated by the circadian pacemaker or by light using quantitative in situ hybridization. The ontogeny of Oct-2 gene expression in the SCN was also studied. Oct-2 mRNA levels remained constant throughout the circadian cycle. In contrast to c-fos mRNA levels which are acutely induced by acute light exposure at night, Oct-2 mRNA levels were not increased by light exposure at night. At gestational day 18, the first age the SCN are anatomically distinct, a prominent Oct-2 hybridization signal was present in the SCN. Our results suggest that Oct-2 is constitutively expressed in the SCN and is present from the time the SCN are discernible as discrete nuclei in fetal brain.


Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion.

Repeated exposure to stressful situations has been shown to increase individual reactivity to addictive drugs. However, the biological factors involved in such stress-induced changes are largely unknown. In this study, we investigated the role of corticosterone in the effects of restraint stress on the response to psychostimulants and opioids. The effects of repeated stress on amphetamine- and morphine-induced locomotor activity were compared in: (i) animals with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) animals in which stress-induced corticosterone secretion was blocked by adrenalectomy, but who received exogenous corticosterone from a subcutaneous implant. The implanted pellets (50 mg) slowly release corticosterone producing a stable plasma level within the normal physiological range over a period of 20 days. Restraint stress increased the locomotor response to both amphetamine (1.5 mg/kg i.p.) and morphine (2 mg/kg s.c.) in animals with an intact HPA axis, but not in animals in which stress-induced corticosterone secretion was suppressed. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress amplifies behavioral responses to amphetamine and morphine. Since an enhanced locomotor reactivity to addictive drugs has been found to be frequently associated with an enhanced vulnerability to drug self-administration, these findings point to a role for glucocorticoids in the susceptibility to drug abuse.


Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons.

Changes in neuropeptide Y-like immunoreactivity (NPYir) in the rat L4 and L5 spinal cord and dorsal root ganglia (DRG) were examined after different sciatic nerve injuries (transection, loose ligation, and crush) and a localized, painful inflammation of the hind paw. Inflammation had no effect on NPYir. All the nerve injuries produced comparable increases in NPYir in ipsilateral laminae III-V axons and varicosities, and induction of NPYir in many DRG cells. Most NPYir DRG cells were medium to large (mean diameters: 40-45 microns); less than 2% of the cells had diameters of 25 microns or less. We conclude that the nerve injury-evoked increase in NPYir occurs mostly in the somata and intraspinal arbors of low-threshold mechanoreceptors; very few, if any, C-fiber afferents are involved. Nerve injury, rather than a painful condition, appears to be the stimulus for the induction of NPYir synthesis.


Continuous amphetamine and cocaine have similar neurotoxic effects in lateral habenular nucleus and fasciculus retroflexus.

Both amphetamine and cocaine lead to an intake pattern in chronic addicts in which the drug is taken repeatedly over prolonged periods. While continuously administered amphetamines, designed to mimic this intake pattern, have a neurotoxic effect on caudate dopamine terminals, several studies have failed to find similar effects following continuous cocaine. In this study, these findings in striatum were replicated in rats using silver staining for degenerating neurons. But it was further found that either amphetamine or cocaine given continuously over a 3- to 5-day period induce a highly specific pattern of axonal degeneration extending from the lateral habenular nucleus along the fasciculus retroflexus towards the ventral tegmentum. This finding supports a rich literature on the involvement of these same pathways in the actions of dopamine agonists, reward mechanisms, and the integration of limbic, extrapyramidal, and midbrain centers.


Rolling mouse Nagoya as a mutant animal model of basal ganglia dysfunction: determination of absolute rates of local cerebral glucose utilization.

In order to elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling), a neurological mutant mouse (genotype rol/rol) showing frequent lurching and falling over on walking, we determined absolute rates of local cerebral glucose utilization (LCGU) with the [14C]deoxyglucose method. The rates were compared with those of heterozygote (+/rol) with normal behavior, and of normal mice (+/+) of the same strain (C3Hf/Nga). Rolling showed marked and significant increases in LCGU in the structures of the basal ganglia such as the globus pallidus, entopeduncular nucleus, substantia nigra pars compacta and pars reticulata, and subthalamic nucleus, confirming our previous finding with semiquantitative LCGU determination. Additional significant but much less marked increases in LCGU of rolling were found in some structures of the brainstem and limbic system, such as the pedunculopontine nucleus, red nucleus, ventral tegmental area, lateral habenula, and CA1 and CA3 of the hippocampus. Although rolling has been regarded as an animal model of cerebellar ataxia, rolling showed no alterations of LCGU in the cerebellum. The heterozygote showed intermediate increases in LCGU between rolling and normal mice in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. Our findings indicate that rolling has a definite, genetically determined dysfunction of the basal ganglia. The primary site of the basal ganglia dysfunction might probably be in the striatum, involving both the neostriatum and limbic striatum, and resulting in secondary dysfunction in their target structures.


Histochemical study of the lumbar colonic nerve supply to the internal anal sphincter and its physiological role in dogs.

The sympathetic innervation of the internal and sphincter (IAS) and its physiological role in maintaining sphincter tone were histochemically and mechanically studied in dogs anesthetized with pentobarbital sodium. Numerous catecholamine-fluorescent nerve fibers with varicosities were identified in the IAS of normal dogs. Such fibers were markedly reduced at one week and one month after resection of the hypogastric nerves (HGNs) or the lumbar colonic nerve (LCN), and disappeared after combined HGN and LCN resection. IAS tone decreased to 37.2% of baseline at 1 h after LCN resection and to 69.9% after HGN resection. It returned to the preoperative level at one week and one month after resection. The restored IAS tone was decreased again by acute transection of the previously intact HGNs or LCN. Combined LCN and HGN resection also caused a marked reduction of IAS tone (36.9%) at 1 h after the procedure, and was then restored to the preoperative level with time. The restored tone was not decreased by phentolamine administration. These findings confirmed that both the LCN and the HGN innervate the IAS and play a physiological role in the development of resting tone. The restoration of IAS tone after denervation may be due to intrinsic myogenic properties of the sphincter.


Intra-amygdaloid infusions of clonidine retard kindling.

It has been reported previously that systemic administration of clonidine, an agonist of alpha-2 noradrenergic receptors, significantly retards amygdaloid kindling by delaying the emergence from partial seizure. We examined the effect of either systemic administration (i.p.) or intra-amygdaloid infusions of clonidine on the kindling of seizures with electrical stimulation of the amygdala. Rats received either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Clonidine and electrical stimulation were administered once every 48 h. We observed a significant retardation of kindling in rats receiving i.p. injections of clonidine (0.1 mg/kg) or infusions of clonidine in concentrations of 10(-7)-10(-4) M, regardless of the stimulation frequency. The prophylactic effect was due to a delay in the progression out of partial seizure. The effect was specific to the amygdala/pyriform region, because infusions of clonidine dorsal to the amygdala were without effect. Intra-amygdaloid clonidine had little effect on established generalized seizures, suggesting that it was producing a genuine prophylactic effect against kindling. We conclude that the subpopulation of alpha-2 adrenoceptors in the amygdala/pyriform region contributes to the antiepileptogenic effect observed after systemic administration of clonidine.


Rostral ventrolateral medullary neurons projecting to locus coeruleus have cardiorespiratory inputs.

This study was designed to characterize some of the properties of the rostral ventrolateral medullary (RVLM) cells with axonal projection to the locus coeruleus (LC) in urethane anesthetized, vagotomized, paralyzed and artificially respirated rats. The vast majority of RVLM units antidromically (AD) activated from LC (RVLM-LC units) were silent and unresponsive to peripheral chemoreceptor stimulation or nociceptive stimulation. Twenty seven spontaneously active RVLM-LC neurons, AD activated from LC with currents below 30 microA (17 +/- 2 microA) were analyzed. AD mapping (n = 18) indicated that the lowest threshold for AD activation occurred within the LC itself. Axonal branching within or close to LC was suggested by the presence of sudden jumps in AD latency. Maximal AD latencies ranged from 7 to 37 ms. Most spontaneously active RVLM-LC neurons displayed marked central respiratory modulation characterized by either a post-inspiratory or an inspiratory pattern. The majority of the tested neurons were affected (excited or inhibited) by brief peripheral chemoreceptor stimulation (N2 inhalation). Most cells were inhibited by raising arterial pressure but none exhibited any detectable pulse synchrony. Reticulospinal sympathetic premotor neurons of RVLM were not found to project to LC (sample of 9) and very few RVLM cells with on-off respiratory discharges appeared to project to LC (2 out of 110). This study suggests that much of the information conveyed by the RVLM to LC could be of a mixed cardiorespiratory nature.


Autoradiographic identification and characterization of sigma receptors in guinea pig brain using [3H]1(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'-oxoethyl) piperidine ([3H]DuP 734), a novel sigma receptor ligand.

The psychotomimetic effects of certain cycloalkyls and benzomorphans that interact with sigma receptors has led to the hypothesis that these sites may be important in the etiology of schizophrenia. DuP 734 [1-(cyclopropylmethyl)-4-(2'-(4''-fluoro-phenyl)-2'-oxoethyl) piperidine HBr] is a novel sigma receptor ligand. The receptor binding specificity and neuroanatomical distribution of [3H]DuP 734-labeled sigma receptors in guinea pig brain were examined using quantitative autoradiography. [3H]DuP 734 binding (10 microM haloperidol displaceable) to slide-mounted sections of guinea pig brain was saturable and of high affinity (Ki = 3.9 nM). Competition studies, under conditions identical to those used to visualize the receptor, yielded the following rank order of potency: DuP 734 > haloperidol > (+)-pentazocine > (-)-butaclamol > DTG > (+)-SKF 10,047 > (+)-3-PPP > (-)-pentazocine > (+)-butaclamol > U50,488H > (-)-SKF 10,047 > cinanserin > PCP >> MK801, sulpiride. High densities of [3H]DuP 734 binding sites displaceable by haloperidol were present in the limbic system, in particular the dorsal and ventral bands of Broca as well as the ventral pallidum. Within the hippocampus, the pyramidal layers were sparsely labeled, while higher densities of binding sites were evident in the dentate gyrus. The frontal cortex, the mammillary complex of the hypothalamus, the central gray and red nucleus of the midbrain, the pontine reticular nucleus, the Purkinje cell layer of the cerebellum and dorsal and ventral horns, as well as the central gray matter of the spinal cord, all showed enrichments of [3H]DuP 734 binding sites. Lower levels of binding were present in the other regions of the cerebral cortex including parietal, pyriform, occipital, cingulate cortex, as well as the basal ganglia, and negligible specific binding was present in the white matter tracts. The kinetic and pharmacological characteristics and distribution of [3H]DuP 734 binding sites in brain are similar to those previously reported for sigma receptors.


Electron microscopic investigation of the cerebral cortex after cerebral ischemia and reperfusion in the gerbil.

Prompt dendritic damage has been observed in the hippocampus of the gerbil brain after transient cerebral ischemia. In the present study, we studied the frontoparietal cortex of the gerbil brain electron microscopically after brief bilateral carotid occlusion to assess the vulnerability of dendritic processes. After ischemia for 5 min, there was swelling of the periphery of dendrites accompanied by swelling of mitochondria, cytoplasmic vacuolation and disintegration of microtubules in layer I, which spread to layer III after ischemia for 20 min. After reperfusion for 3-24 h following ischemia for 20 min, swelling in the periphery of dendrites and of mitochondria inside receded but vacuole formation and disintegration of microtubules propagated proximally. In neuronal perikarya, polyribosomal disaggregation was observed after ischemia for 20 min and persisted thereafter, while fragmentation of rough endoplasmic reticulum (ER) and microvacuolation occurred after reperfusion for 3 h. Electron-dense clumping of neuronal perikarya was observed after reperfusion for 6 h particularly in layers III and Vb, which increased in number for up to 72 h. The observed progressive damage in dendrites may be common to neurons vulnerable to cerebral ischemia and may significantly contribute to development of delayed neuronal death.


Central sites mediating reproductive responses to melatonin in juvenile male Siberian hamsters.

Juvenile male Siberian hamsters received infusions of varying doses of melatonin (MEL), or saline vehicle, via microdialysis probes implanted in brain regions which have previously been shown to contain MEL receptors. Daily infusions were 10 h in length and occurred during exposure to constant light on days 22-34 of age. All animals were sacrificed on day 35 and paired testis weights recorded prior to preparation of the brain tissue for histological evaluation of the infusion site. Some animals were also blood-sampled prior to sacrifice for determination of circulating levels of prolactin (PRL). Saline infusions did not have a significant effect upon gonadal maturation, regardless of the infusion site, when compared with unoperated control animals reared under similar photoperiod conditions. In contrast, animals which received infusions of 75 pg MEL into the suprachiasmatic nucleus (SCN), paraventricular nucleus of the thalamus, or nucleus reuniens regions, showed a marked inhibition of gonadal growth. Infusions of this dose of MEL into various other neural regions (e.g. lateral hypothalamus, ventromedial nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus) did not result in decreased testis weights at the time of sacrifice. Daily administration of 20 pg MEL inhibited gonadal maturation and resulted in decreased circulating PRL levels only when infused into the SCN region. For animals receiving the 7.5 pg dose, infusions into the midline thalamic nuclei were not successful in inhibiting testis growth, and infusions in the SCN region had only a marginal effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Children's eyewitness memory: effects of participation and forensic context.

We examined effects of participation and forensic context on 4-year-old children's testimony. Children in "participant" and "police" conditions actively participated in games with a "babysitter"; each child in the "observer" condition watched a videotape of a child and the babysitter playing. Eleven days later, children were individually questioned about the event. Before the interview began, children in the police condition talked to a police officer who said the babysitter might have done something bad. Comparison of participant- and observer-condition performance indicated that participation increased free-recall accuracy concerning actions that took place and lowered suggestibility. Comparison of participant- and police-condition performance indicated that forensic context led to increased error in free recall and additional comments to misleading questions. However, forensic context also resulted in higher accuracy on an age-identification task and did not affect children's accuracy in answering abuse-related questions.


Predictors of legal intervention in child maltreatment cases.

Using information extracted from child protective services and criminal court records, this research examines the extent and nature of dependency and criminal filings in 833 substantiated intrafamilial child abuse and neglect cases reported in Denver (CO), Los Angeles (CA), and Newcastle (DE) Counties in 1985-1986. Techniques of chi-square and discriminant analyses were used to identify factors associated with dependency and criminal filings. Results indicate that legal intervention is rare: Dependency filings and prosecutions occur in just 21% and 4% of the sample, respectively, although treatment plan development and out-of-home placement of the child occur in approximately 75% and 50% of the sample, respectively. Eighty percent of cases with criminal filings proceed to trial or plea bargaining, with 92% resulting in conviction. Bivariate analyses indicate cases involving abandonment, sexual abuse, frequent maltreatment, and severe maltreatment are most likely to result in an initial dependency filing, while cases involving sexual abuse, severe maltreatment, a nonparent perpetrator, an ethnic minority perpetrator, a female victim, and a victim aged 7-12 years are most likely to result in a criminal filing. The multivariate analyses show the primary predictor of both dependency and criminal filings is whether the case involved sexual abuse. This finding reflects the widespread public and professional attention child sexual abuse has received in recent years.


Children of torture victims: reactions and coping.

The aim of this study was to describe mental reactions and coping strategies among children of torture victims. The study comprised 11 children from 5 exiled families with at least one of the parents having been subjected to torture. Investigation methods applied were qualitative interviews in three different settings and two projective tests. The children were anxious, depressive, and regressive. Moreover, they presented psychosomatic symptoms, sleep disorders, and family and school problems. The children's ways of dealing with their experiences were divided into four main coping strategies: (a) isolation and withdrawal, (b) mental flight, (c) eagerness to acclimatize, and (d) strength of will and fighting. A lack of flexibility in the children's development of coping strategies was mainly explained by the strength of challenges in the families' overall situation before and after escape and exilation. A lack of openness about imprisonment and torture seemed to be an essential way of parental coping. The observation methods chosen all proved to be applicable and informative. Moreover, the qualitative interview showed to be the crucial method.


The prevalence and context of family violence against children in Finland.

The prevalence and context of violence against children in their families was surveyed as part of a study on the sexual abuse of children. A random sample of 409 comprehensive school classes with approximately 9,000 15-year-olds was asked to anonymously fill out questionnaires. The majority filled out the questionnaires in the privacy of the school nurse's office, the rest in their classrooms. Of the selected classes, 88.8% participated in the survey, and the response rate of the students in those classes was 96%. Mild violence (slapping, pushing, etc.) was reported by 72% of the respondents, and severe violence (hitting with a fist, kicking, use of weapons) was reported by 8%. Violence was committed by the parents sometime before the children reached age 14. Incidents of violence during the year preceding the survey were reported by 19% and 5%, mild and severe, respectively. Mild violence was committed slightly more often by mothers than fathers. Severe violence was perpetrated more frequently by fathers. Girls reported mild abuse more often than boys. Severe violence was experienced equally often by both sexes. Children living with single mothers reported less-than-average mild violence, but more frequent severe violence. The highest incidence of severe violence was found among youth living in families with a stepfather. Unemployment in a family tended to increase both mild and severe violence. Violence was reported least often by children living in farming families or Swedish speaking families (which make up about 6% of Finnish population). Overall the frequency of violence toward children in Finland is significantly lower than in the U.S. Comparison to Sweden seems to show an identical level of child abuse, although different study methods make comparisons difficult.


Early indicators of pathological dissociation in sexually abused children.

Although reported cases of adult multiple personality disorder (MPD) are increasing, confirmation of MPD and related dissociative disorders in children remains rare. Since MPD can cause severe impairment and psychological distress, and is thought to originate in childhood, early recognition of pathological dissociation and predictors of MPD is critical. Sexual abuse in childhood has similarly been under-reported until recently, and is highly associated with the development of dissociative disorders. This paper reviews factors in the professional neglect of these syndromes as well as recent diagnostic developments in childhood dissociative disorders. The identification of subtle dissociative symptomatology in children is illustrated and two case examples are presented.


Gardnerella vaginalis infection and sexual contact in female children.

Gardnerella vaginalis (GV) infection has been reported as being acquired via sexual contact in adults and as an indicator of sexual contact in female children (DeJong, 1985). The purpose of this study was to determine if GV infection was more commonly found in 191 female children who gave a history of sexual contact and/or were infected with Neisseria gonorrhoeae (GC) or Chlamydia trachomatis (CT) (Group 1), compared with 144 female children evaluated for possible sexual abuse and found to have no such history or infection with GC or CT (Group 2), or 31 female children (friends of the authors) without such a history or GC or CT infection (Group 3). Vaginal GV was found in 5.3% of Group 1, 4.9% of Group 2 and 6.4% of Group 3 (p > .05). Also, vaginal GV infection was not related to the type of sexual contact or race, but did increase with age in white female children. Because vaginal GV infection is not more commonly found in children with a history of sexual contact than those without such a history, the finding of GV in a vaginal culture in an individual case would not be a reliable marker of sexual contact. Routine culturing for GV is not recommended as part of a sexual abuse workup.


The pattern of sugar consumption in social class groups of young adolescents in Northern Ireland.

The pattern of sugar consumption in a sample of 350 11-12-year-old adolescents was examined. Their knowledge of the sugar content of a range of common foodstuffs was also investigated. There were only small differences between the social class groups in mealtime sugar consumption. The frequency of total food and drink was significantly higher in the low social class groups and this was mainly explained by significantly higher between meal consumption of solid food which contained sugar. The level of knowledge of the sugar content of foods was significantly higher in the higher social class groups. Fifty-two per cent of the questions were answered correctly, with a range of 9-91 per cent for individual foodstuffs.


Sexual abuse prevention education for young children: a comparison of teachers and parents as instructors.

The purpose of this study was to compare teachers and parents as instructors of a personal safety program. One hundred seventy-two Head Start preschoolers were randomly assigned to a personal safety program taught by their teachers, parents, both teachers and parents, or to a general safety control program. Following program participation, children taught the personal safety program by their teachers, parents, or both, demonstrated greater knowledge about sexual abuse and higher levels of personal safety skills compared with those in the control group. Gains in knowledge and skills were maintained at the 5-month follow up. Children taught by their parents showed greater improvements in recognizing inappropriate-touch requests and in their personal safety skills compared with children taught by their teachers, and children who received the program both at home and school were better able to recognize appropriate-touch requests and to demonstrate higher levels of personal safety skills compared with children taught only at school. The emotional costs associated with participating in the program were minimal, and both parents and children rated the program positively. The advantages of home-based instruction for young children are discussed and suggestions for future research are offered.