Management of chronic rumination with a contingent exercise procedure employing topographically dissimilar behavior

Walking was employed as a functionally incompatible activity in a contingent exercise procedure to manage chronic rumination in a 10 year old mentally retarded male. The high frequency ruminative behavior was rapidly reduced once the topographically dissimilar activity was introduced as a contingency. On the first day the contingent exercise procedure was used in conjunction with a differential reinforcement of other behavior (DRO) 30-sec schedule. Thereafter the contingent exercise was used alone. The ruminative behavior appeared to be under the control of the contingency and remained at essentially a zero rate during the 4 month extended observation period as well as throughout the 6 month follow-up     

GABA synthesis in isolated vestibulary tissue of chick inner ear

This study was undertaken to assess the possible participation of GABA in neurotransmission in the inner ear of higher vertebrates utilizing isolated chick vestibulary cristae as a model. GABA synthesis was investigated as a suitable criterion for postulating this amino acid as a putative neurotransmitter. Enzyme-mediated GABA synthesis was demonstrated implying a possible neurotransmitter role of this amino acid in the chick vestibule.     

Restlessness of respiration as a manifestation of akathisia: five case reports of respiratory akathisia

BACKGROUND: Akathisia is a feeling of subjective or inner restlessness, which causes excessive, semipurposeful movements, commonly in the legs. However, restlessness in respiration, which presents as dyspnea but is best characterized as the sensation of being unable to breathe in a relaxed manner, has never been reported. CASE REPORTS: Five cases are reported in which dyspnea as a sign of akathisia followed the administration of antipsychotic medications. The clinical features of dyspnea were examined, and all patients manifested both subjective and objective restlessness. The dyspnea was characterized subjectively by the patients' inner feeling of restlessness in respiration, which was perceived as an inability to breathe in a leisurely, relaxed manner, and objectively as restless movements of respiration such as gasping or sighing. The dyspnea was momentarily suppressed when a patient took a quick, full breath to relieve the perceived restlessness and was exacerbated when the patient kept the respiration still. Response to medications commonly used in the treatment of akathisia was also examined in an open, uncontrolled therapeutic trial for each patient. The administration of such medications completely alleviated the respiratory restlessness. CONCLUSION: Restlessness in respiration, which clinically presents as dyspnea, may be a manifestation of akathisia. This type of akathisia could be referred to as respiratory akathisia.     

Neurological, neuropsychological, and functional outcome following treatment for unruptured intracranial aneurysms.

The objective of this study was to carry out a detailed investigation of the neurological, neuropsychological, and return-to-work status of treatment for unruptured intracranial aneurysms (UIAs). A prospective design was used to evaluate the outcome of UIA treatment in a group of 26 UIA patients. Over a 24-month period UIA patients were assessed prior to treatment, during hospitalization, at three months and at six months following treatment. Their performance was compared to a group of 20 matched controls. Neurological morbidity as a result of the UIA treatment was 5%, as assessed by the Glasgow Outcome Scale (GOS) or Rankin at 3 months. The Telephone Interview for Cognitive Status (TICS) proved to be unreliable as a measure of cognitive change. Reliability of change analysis was more sensitive than group analysis, and revealed a pattern of cognitive deficits in 10% of patients as a result of the UIA treatment. In addition, 25% of patients reported a change in work role as a result of the UIA treatment. While 10% of patients sustained mild to moderate neurological and cognitive impairments 3 to 6 months following UIA treatment, their deficits were not as wide-ranging nor as severe as those sustained by patients who survive a subarachnoid hemorrhage (SAH).     

Development and utilization of the patient knowledge questionnaire on botulinum toxin use in movement disorders.

Following a pilot study, the 28-item Patient Knowledge Questionnaire on Botulinum Toxin Use in Movement Disorders (PKQ-BMD) was utilized to assess efficacy of current educational tools by comparing scoring of patients to that of the general population, as well as to identify information resources, target demographics for education, and key counseling topics. Of the 109 participants, the number of correct answers was higher in the patient group, while the number of incorrect answers was low in both groups. Education was the only demographic factor which affected the total score. The primary source of patient information was their neurologist, and "adverse effects" was perceived as the most important educational topic. We conclude that the PKQ-BMD is a valuable instrument for knowledge assessment, as well as a tool for developing more effective patient resources.     

The scientific status of neurotic depression

The concept of neurotic depression was introduced in the early part of the 20th century. The concept has undergone many revisions, and recently was discontinued as a category in the DSM-III. In the past, neurotic depression was referred to as a nonpsychotic form of depression, a nonendogenous depression, as well as many other categories. The presence of various meanings has made it difficult to develop algorithms for neurotic depression; the findings substantiate the decision of the DSM-III not to continue the category of neurotic depression.     

The acute histopathology of MPTP in the mouse CNS

We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rapidly induced cytopathological changes in the brain, involving some neurons selectively, as well as astrocytes and blood vessels. Dopaminergic neurons in the midbrain, as identified by immunostaining for tyrosine hydroxylase, were damaged as early as 2.5 hr after MPTP administration. Ultrastructurally, there was disruption of the endoplasmic reticulum and cytoplasmic condensation and vacuolation of the tyrosine hydroxylase reactive neurons in the substantia nigra as well as their axon terminals in the striatum. Perivascular edema was associated with vacuolation and swelling of astrocytic cytoplasm and rupture of perivascular foot processes. There was also capillary and arteriolar endothelial damage. Surprisingly, there was no clear correlation of MPTP-induced pathology with mitochondrial damage in any cell type. Biochemically, dopamine was depleted in the substantia nigra and the striatum within a few hours following MPTP administration. However, in the substantia nigra, homovanillic acid (HVA), one of the metabolites of dopamine, showed relatively less depletion than did dopamine by MPTP. These results may indicate that the turnover of dopamine was stimulated in the brain as a homeostatic mechanism.     

Phagocytic astrocytes and neurons in old encephalomalacia.

Cytoplasmic accumulation of hemosiderin was observed within astrocytes and neurons as well as in other phagocytes associated with old encephalomalacia. The first patient was 3 years old when she died with malnutrition and superimposed infection. A cortical infarct had been caused by an old thrombus in a small artery. The second case was a 9-year-old girl who had old encephalomalacia in the pineal region after extirpation of a pineoloma. The third patient was a 22-year-old man who had a cortical infarct from an embolus associated with chronic rheumatic endocarditis. Granules of hemosiderin had accumulated within the perikaryon of many astrocytes and other phagocytes in all cases, and in a few neurons in the second instance. Review of the literature reveals that cytoplasmic accumulation of particulate matter has been described infrequently with regard to neuroepithelial derivatives. Our findings indicate that astrocytes and neurons as well as derivations of mesenchyme may act as phagocytes of old blood.     

A psychiatric and social matched case series comparison of victims of criminal homicide and homicide perpetrators in Sweden

The aim of the present study was to compare the psychosocial profiles of criminal homicide victims with those of a matched sample of perpetrators. The hypothesis was that chance determines whether someone becomes a victim or a perpetrator. In a retrospective examination of forensic psychiatric records as well as hospital records, the following variables were studied: nationality, education, substance abuse and psychiatric diagnoses. A comparative study was performed of 88 perpetrators and 83 victims in Sweden during a time period of 17 years (1978-1994). All subjects had been treated as psychiatric inpatients before the homicide. The results support the hypothesis that perpetrators and victims of homicide are similar with regard to psychiatric morbidity and social functioning. The majority were born in Sweden, and the educational level was low in both groups. Substance abuse was common in both groups: 96.7% of male and 65.3% of female victims compared with 76.6% of male and 75% of female perpetrators. Many in both of the groups had criminal records. The only major difference between the groups was recorded for psychotic disorder diagnoses, with a higher rate among perpetrators as well as a lower rate of substance abuse in this group.     

An ultrastructural study of the vascular and muscular basement membrane in Duchenne-type dystrophy

The ultrastructural distribution of basement membrane around the capillaries as well as muscle cells of boys with Duchenne-type muscular dystrophy was determined. In dystrophic muscles, a diffuse thickness of vascular as well as muscular basement membrane was observed. Lamina densa lost its regular ribbon-like appearance and was split into several thin layers. After staining with tannic acid (TA), a densely stained meshwork was present on the muscle cell surface as well as in the extra-cellular space. Hyaluronidase treatment removed TA-stained deposits, indicating that hyaluronic acid is a major component. Enzyme resistant structures, presumably fibrous long-spacing collagen fibrils, have been found in dystrophic muscles. Based on the results of the study, faulty structure of the basement membrane in dystrophic muscle is suggested.     

Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia

The purpose of this study was to investigate the role of fas antigen, a member of the TNF receptor family, in cell death after focal cerebral ischemia. Focal ischemia was induced in the Sprague-Dawley rat. Evidence for apoptosis was determined by morphology as well as the presence of DNA fragmentation by the end labeling technique (TUNEL). Immunohistochemistry was performed to detect expression of both fas and fas ligand (fasL). In a separate set of experiments, two groups of mice were studied: lpr (that have a loss of function mutation for fas) and wild type. Infarct volume was measured at 24 hr as well as evidence for apoptosis. Twenty-four hours after ischemia, there was evidence for apoptosis based on morphological criteria as well as the TUNEL technique in the rat. Immunohistochemistry demonstrated increased expression of both fas and fasL in the ischemic region, with maximal staining occurring between 24-48 hr for both. Twenty-four hours after ischemia in the mice, there was evidence of apoptosis in both groups, however, the mutant mice (lpr) had significantly smaller infarcts as compared to the wild type. There was no difference in the cerebrovasculature of the two groups of mice. These data support the hypothesis that apoptosis plays a role in the pathophysiology of focal cerebral ischemia. Furthermore, these data suggest that fas-mediated apoptosis contributes to this process.     

Regional cerebral blood flow correlates of language processes in reading disability

This series of studies tests the hypothesis of abnormal left hemisphere activation in reading-disabled subjects during language task performance. First, a left superotemporal focus of activation, as measured by regional cerebral blood flow, was found to be positively correlated with task accuracy in a group of 69 normal adults. Next, that left superotemporal activation was replicated in a second group of 83 adults whose childhood reading ability was known from standardized tests given in childhood. Finally, in that latter group, childhood reading ability was also found to be inversely correlated with focal activation in a more posterior, temporoparietal area of cortex. Adult reading outcome was statistically unrelated to this finding. The results are interpreted as suggesting a trait anomaly of left hemisphere cerebral activation in adults who were dyslexic as children and as providing an existence proof of individual differences in focal cortical activation sites during constant task demands.     

Acute changes in cerebral oxygenation and cerebral blood volume in preterm infants during surfactant treatment.

Following administration of surfactant a marked depression in aEEG activity occurs for about 10 minutes; the mechanism of this depression is unknown. In view of this, twenty-nine preterm infants were investigated with near infrared spectroscopy (NIRS) to evaluate rapid changes in total cerebral haemoglobin concentration and cerebral oxyhaemoglobin concentration during rescue treatment with natural surfactant. During surfactant instillation there was a short-lasting hypoxaemia as demonstrated by pulseoximetry as well as a considerable fall in arterial blood pressure. With NIRS, tissue hypoxia was demonstrated by a drop in cerebral oxyhaemoglobin concentration. The marked drop in arterial blood pressure occurring immediately following surfactant was not matched by a drop in total cerebral haemoglobin concentration. This suggests that cerebral blood volume and hence cerebral blood flow was maintained. In the following minutes there was an improvement in cerebral oxygenation as indicated by the rise in cerebral oxyhaemoglobin concentration in nearly all the infants.     

Reactivity of factor VIII inhibitors in a micro ELISA for factor VIII: CAg and in solid phase immunoisolation of VIII: CAg

Factor VIII coagulant antigen (VIII: CAg) was measured in a sandwich-ELISA. Microplates were used as solid phase and peroxidase conjugated F(ab')2 fragments of IgG isolated from inhibitor plasma was used as label without affinity purification. The capacity of the assay was high and the sensitivity for VIII: CAg was 0.002 U/ml. Using this assay it was possible to measure coagulation inactive VIII: CAg in samples from purification studies. Below 0.05 VIII: CAg U/ml these samples responded in parallel with standard plasma. Seven of 7 inhibitor antibodies tested were able to inhibit binding of peroxidase-conjugate in the VIII: CAg assay, and the inhibitory capacity correlated with coagulation inhibition as measured by the Bethesda method. Using the highest titered antibodies bound to a solid phase, VIII: CAg was isolated and identified in SDS-PAGE as a doublet with a molecular weight of 77-80 kD.     

Determination of lipoprotein (a) [Lp(a)] in patients with ischemic stroke. Preliminary communication

The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the patients three months after the onset of ischaemic stroke. A group of 56 patients was investigated. Stroke was diagnosed as caused by atherosclerotic changes in main cerebral arteries in 32 patients and in 11 by changes in cervical arteries. In 13 persons a lacunar stroke was recognised. The mean Lp(a) level and the median value were significantly higher in the group of patients after stroke as compared with 45 controls. A more frequent occurrence of Lp(a) level over 30 mg/dl considered as pathological was observed more often in the patients. No correlation was seen between Lp(a) and the resistance of LDL to oxidation nor between Lp(a) and the amount of products of LDL oxidation in vitro.     

Early contingent negative variation (CNV) shows a small symmetrical negativity in a somatosensory paradigm.

The influence of sensory modulation on the early stage of information processing was investigated with a somatosensory contingent negative variation (CNV) paradigm. Whether or not even a somatosensory input as well as auditory or visual stimulus to one hemisphere elicits the symmetrical "early CNV" was also examined. Eleven normal individuals (3 males, 8 females) performed a conventional CNV paradigm with a click sound as the warning stimulus (WS) and a red light flash as the imperative stimulus (IS). Nine individuals (5 males, 4 females) did the somatosensory CNV paradigm with paired electrical stimuli as WS and IS. The subjects were instructed to press a button in response to IS as fast as possible. The early CNV amplitude was smaller and P300 latency was longer in somatosensory paradigm than conventional paradigm. In addition, the latency of P100 in a somatosensory paradigm was longer than that of N100 in a conventional paradigm. These findings suggest that the initiation of early detection, reflected by P100, the initiation of cognition, reflected by P300, and orienting response, reflected by early CNV, are delayed in a somatosensory CNV paradigm. Furthermore, all event-related potentials (ERPs) evoked by somatosensory stimuli showed a bilateral symmetry.     

Effects of thyroid dysfunction on the development of the rat cerebellum, with special reference to cell death within the internal granular layer

The increased cell death within the internal granular layer of the cerebellar cortex, previously demonstrated by other investigators in 12-day-old rats treated with propylthiouracil, was found again in 10-, 14- and 21-day-old similarly treated young rats. In thyroid-deficient as well as in normal animals, cell death was maximal at 10 days. In hypothyroid rats, the greatest difference with the normal animals was at 14 days, when there was an increase by a factor of 20 of the number of dying cells. On day 13, the ratio of free to total N-acetyl-β-d-glucosaminidase activities was also increased by 34%. Cell death predominantly occured in the lower part of the internal granular layer at 10 days, in the middle part at 14 days and the upper part at 21 days. The increase in thickness of the molecular layer, which reflects the development of the Purkinje cell dendritic arborizations, was also more retarded than the acquisition of a normal ratio of granule cells to Purkinje cells. Administration of a daily dose of 0.10 μg thyroxine to thyroid-deficient animals was sufficient (and a lower dose insuffucient) to return to normal the number of dying cells as well as the development of the molecular layer and the evolution of the ratio of granule cells to Purkinje cells. A daily dose of T4 as low as 0.20 or 0.25 μg already induced a marked hyperthyroid state resulting in a decrease in granule cells formation without increased cell death. Indeed, an increased cell death seemed to occur only when the normal synchronism between the development of the Purkinje cell arborizations and the laying down of granule cells was suppressed, as is the case in thyroid deficiency but not in neonatal hyperthyroidism.     

Comparative study of paroxetine and mianserin in depression in elderly patients: efficacy, tolerance, serotonin dependence

The primary objective of this multicentre, randomized, double-blind study carried out in France was to compare the efficacy and safety of a 6-week treatment with paroxetine (20 mg/day) or mianserine (30 mg/day) in geriatric hospitalized or ambulatory patients (> or = 60 years) treated for a major depressive disorder (according to DSM III-R). A secondary objective was to discriminate those items predicting the response to an agent according to its serotoninergic or noradrenergic pharmacologic profile. The tool used for this latter purpose was the Aubin-Jouvent-Rating-Scale (AJRS) which was designed to assess the deficit of serotonin: this is a scale with 10 items, some of them regrouped into a "general" factor (irritability, sudden mood change, impatience, aggressivity) or a "depression" factor (pain, anxiety, suicidal ideas) with additional items related to sleep disorders, abnormalities in eating behavior and inability to tolerate isolation. In the perspective of this assessment, paroxetine was chosen due to its potential to inhibit serotonin re-uptake, as compared to mianserin which blocks presynaptic alpha-adrenergic receptors with negligible action on serotonin. This was a multicenter study carried out in France in 50 hospital or private practice psychiatrists. The assessment criteria included the MADRS, the AJRS, the COVI's anxiety scale, the Folstein's Mini-mental state (MMS) as well as a global assessment by the investigator at the end of the study. Safety was measured with a nondirective questionnaire, routine laboratory tests as well as a global assessment by the investigator. The primary efficacy criteria was the change in the MADRS global score. Statistical analysis included chi-square or Fisher's test as well as Student's and Wilcoxon tests for comparability at baseline, and analysis of variance for the changes in scores as during the study. A total of 116 patients was randomised (paroxetine: 54; mianserine: 62), of whom 96 completed the study (paroxetine: 43; mianserine: 53). With the exception of MADRS moderately higher in the paroxetine group, both groups were comparable at baseline. After 6 weeks of treatment, a marked improvement was recorded in both groups for all criteria except MMS; there was a consistent tendency favouring paroxetine which reached statistical significance for the COVI' scale (p = 0.001). For a given criterion, the difference paroxetine versus mianserine appeared related to the score at baseline; it was also more marked in those patients with a AJRS baseline score > or = 20 with a difference for MADRS reduction of marginal significance in favor of paroxetine (p = 0.061). As regards safety, at least one adverse event was reported in 31.5% of the patients receiving paroxetine versus 41.9% in those receiving mianserin (NS); premature withdrawal related to an adverse event was reported in 11.1% of the patients in the paroxetine group versus 12.9% in the mianserin group. No abnormality of clinical significance was reported in either group concerning laboratory tests. In conclusion, this study confirmed the therapeutic value and good safety of paroxetine as an antidepressant in geriatric populations, especially when exist a concomitant anxiety or symptoms likely to reflect a deficit of serotonine (irritability, emotional lability, restlessness, aggressivity) and to predict a good response to an agent such as this one.     

Evidence of subnormal function of association cortex in presenile dementia.

Regional cerebral blood flow (rCBF) was measured in 23 patients with organic dementia (17 patients with Alzheimer's disease and six with low-pressure hydrocephalus [LPH]). The flow of gray matter was significantly reduced, especially in occipito-parieto-temporal regions, as well as frontally in some patients. During activation with psychologic tests, reading, etc., the flow augmentation in the association areas in the demented patients was not as marked as in nondemented controls. Instead, in some patients, a flow diminution was recorded in the same regions (intellectual steal). Organic dementia appears to be accompanied by a low activity in the association cortex and a reduced ability to activate these regions during mental effort.     

The token economy in day hospital settings: Contingency management or information feedback

The token economy was evaluated as a contingency management system with chronic psychiatric patients in a day hospital setting. The hospital population was considered an N of 1, and the results were evaluated in a single case experimental design. Patients' performance in the token economy remained essentially the same whether the contingencies were in effect or not. A self-report questionnaire administered in phase 3 indicated that most patients viewed points earned as indicating how well they were doing in the program as opposed to allowing them to purchase various rewards. The token economy as a feedback system in a day hospital was discussed.