A sandwich enzyme linked immunosorbent assay to detect rabies antibodiesin sera of different species

A sandwich ELISA (S-ELISA) was developed to detect antibodies to rabies virus in seraof different species. The test was performed as follows: ELISA plates were coated withpolyclonal mouse/anti-rabies antibodies for 2 hours at 37ºC. After adsorption, plateswere washed and non-specific binding blocked with 2% powdered milk. In a separateplate, serial threefold dilutions of test sera were incubated with inactivated rabies virusantigen. The mixtures were then placed on the rabies antibody-coated plates andincubated. These were then washed and incubated with polyclonal rabbit/anti-rabiesantibodies. Subsequently, a rabbit/IgG-peroxidase conjugate was added and platesincubated. After washing, the chromogen (ABTS with 0.15% H2O2) was added to platesand after incubation for 30 min were read in a spectrophotometer (OD405). To validatethe S-ELISA, 128 serum samples including humans, cattle, hematophagous and nonhaematophagous bats, mice, marmosets, ocelots - Leopardus pardalis, raccoons -Procyon lotor, jaguarondi - Herpailurus yaguarondi, fox - Cerdocyon thous and coati -Nasua nasua, were tested and compared to a standard fluorescent antibody virusneutralization test (FAVN). In comparison to FAVN, the S-ELISA showed highsensitivity (82.98%) and specificity (100%), with an accuracy of 87.5%. Subsequently,738 serum samples from different species were tested in the S-ELISA. Antibodies torabies were detected by S-ELISA in all species tested, with the exception of the threeserum samples from raccoons. The S-ELISA was shown to be a serological test of lowcost that can be easily implemented in diagnostic laboratories. In addition, no liveanimals, infectious virus, cell culture or fluorescence microscopy are required forperformance of the test. This is an additional advantage of the S-ELISA over othermethods of rabies antibody detection.

Long-term effects of cannabis on oculomotor function in humans.

Cannabis is known to affect human cognitive and visuomotor skills directly after consumption. Some studies even point to rather long-lasting effects, especially after chronic tetrahydrocannabinol (THC) abuse. However, it is still unknown whether long-term effects on basic visual and oculomotor processing may exist. In the present study, the performance of 20 healthy long-term cannabis users without acute THC intoxication and 20 control subjects were examined in four basic visuomotor paradigms to search for specific long-term impairments. Subjects were asked to perform: 1) reflexive saccades to visual targets (prosaccades), including gap and overlap conditions, 2) voluntary antisaccades, 3) memory-guided saccades and 4) double-step saccades. Spatial and temporal parameters of the saccades were subsequently analysed. THC subjects exhibited a significant increase of latency in the prosaccade and antisaccade tasks, as well as prolonged saccade amplitudes in the antisaccade and memory-guided task, compared with the control subjects. The results point to substantial and specific long-term deficits in basic temporal processing of saccades and impaired visuo-spatial working memory. We suggest that these impairments are a major contributor to degraded performance of chronic users in a vital everyday task like visual search, and they might potentially also affect spatial navigation and reading.

Psychiatric symptoms in a patient with Wolfram syndrome caused by a combination of thalamic deficit and endocrinological pathologies.

DIDMOAD or Wolfram syndrome is a hereditary disorder characterized by early onset diabetes and optic atrophy. Besides these features, a variety of other symptoms have been described including psychiatrical abnormalities leading to hospitalization in about 25% of all patients. To our knowledge, until now, a detailed characterization of these psychiatric symptoms does not exist. Here we describe a 21-year-old male patient with deficits of frontal lobe function, such as impaired impulse control and learning deficits. Magnetic resonance imaging (MRI) of the brain showed a bilateral optic atrophy, but no signs of frontal brain atrophy. Neuropsychological tests revealed performance deficits in complex planning (e.g., Tower of London). Also his capacities in memorizing logically connected information after a short and delayed period of time were significantly reduced. Since histopathological studies did not reveal frontal brain abnormalities, but did show thalamic neuronal loss and gliosis, we interpret our findings as representative of thalamic dysfunction. In addition, hypoglycaemia seemed to trigger rapid mood swings. As soon as blood glucose levels improved, the patient stabilized emotionally and assaultive behaviour disappeared while the cognitive deficits remained unchanged.

Neuropsychological and behavioural disinhibition in adult ADHD compared to borderline personality disorder.

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) is thought to be an inhibitory disorder, the question remains of how specific the inhibitory deficit is in adults and whether it distinguishes ADHD from borderline personality disorder (BPD), with which it shares several clinical features, particularly impulsiveness. METHOD: The study assessed various motor and cognitive inhibitory functions (inhibition of prepotent, ongoing and interfering responses) in addition to working memory in adult ADHD patients with and without BPD, compared to subjects with BPD alone and controls. In addition, questionnaire data on various aspects of impulsiveness and anger regulation were assessed in all groups. RESULTS: ADHD patients performed worse than BPD individuals and controls in two inhibitory tasks: the stop signal task and the conflict module of the Attentional Network Task (ANT). In addition, they exhibited longer reaction times (RTs) and higher intra-individual variance in nearly all attentional tasks. The co-morbid group exhibited poor performance on the stop signal task but not on the conflict task. The BPD group barely differed from controls in neuropsychological performance but overlapped with ADHD in some behavioural problems, although they were less severe on the whole. CONCLUSIONS: Impaired inhibition is a core feature in adults with ADHD. In addition, slow RTs and high intra-individual variance in performance may reflect deficits in the regulation of activation and effort in ADHD patients. ADHD and BPD share some symptoms of behavioural dysregulation without common cognitive deficits, at least in the attentional realm.

[Cognitive impairment after accidental high-dose corticosteroid therapy]. / Kognitive Störungen nach akzidenteller hoch dosierter Kortisontherapie.

Synthetic glucocorticosteroids can induce various severe mental disorders. Persisting cognitive disorder represents a rare complication of corticoid therapy involving memory, concentration, attention, or occupational performance. We observed the effects of a 20-day self-induced high-dose corticosteroid treatment on the cognitive functions in a 54-year-old patient. Having excluded dementia due to other organic causes, we examined the patient neuropsychologically immediately at the end of the steroid therapy and at follow-up (1, 2, 4, and 6 months). The initial tests showed seriously impaired functioning of concentration, attention, learning, and memory as well as of common ability to solve problems. The follow-up tests up to 6 months revealed an improvement of concentration and attention, but there were still serious deficits of the declarative memory with a high confabulating tendency. Our results confirm those of human experimental studies that exogenous steroids can cause serious persisting specific cognitive disorders especially of the declarative, hippocampus-dependent memory.

Depth profiling of high-energy hydrogen-implanted 6H-SiC.

The results of implanting silicon carbide with a 1-MeV proton beam at a dose of 1 x 10(17) cm(-2) are presented. Using high-resolution confocal Raman spectroscopy, we analyzed the depth profile of the implantation damage before and after thermal annealing. When it is applied to a high-refractive-index medium, such as SiC, this technique requires careful manipulation to ensure the correct interpretation of results. To this end we discuss a simple ray-tracking model that includes the effects of additional spherical aberration and of the Gaussian intensity profile of the excitation beam. In addition, infrared reflectance measurements show evidence of a well-defined step in the refractive-index profile at the expected implantation depth.

Auditory-evoked potentials and selective attention: different ways of information processing in cannabis users and controls.

The present study tested the hypothesis that chronic cannabis use leads to persistent attentional dysfunctions and that age of onset of cannabis use is a potential predictor of impaired test performance and information processing. Brain event-related potentials (ERPs) during a complex auditory selective attention task were recorded from 21 cannabis users divided into two groups according to age of onset and from 13 controls comparable with respect to age, IQ and educational background. Participants were instructed to detect target tones of a particular location, pitch and duration from a total sample of random frequencies. The study reveals that the latency of the greatest negative peak of ERPs (200 and 300 ms) to target tones was shorter in controls, while there was no clear difference between target and non-target within cannabis users. In addition, users displayed a reduced P3 to target tones. This was more pronounced in early-onset cannabis users. These data suggest that chronic cannabis use relates to different types of information processing under conditions of selective attention. There is some evidence that users employed different strategies of attention allocation. The results are discussed with respect to possible underlying mechanisms and clinical implications.

Impaired and enhanced attentional function in children with attention deficit/hyperactivity disorder.

BACKGROUND: The symptom domain of inattention in attention deficit/hyperactivity disorder (ADHD) suggests that there are neuropsychological fields of attention in which subjects with ADHD express deficits. However, studies using differentiated neuropsychological attentional tests in ADHD are lacking. METHOD: A consecutive series of 35 subjects with ADHD aged 9-12 years were assessed on a computer-driven neuropsychological test battery for attentional functions. Their performance was classified according to the data of a normative sample of 187 healthy subjects aged 9-12 years, and compared with the performance of 35 matched healthy control subjects. RESULTS: According to normative data, most ADHD subjects performed on all attentional measures within the normal range. Comparisons with the control group revealed that ADHD subjects reacted faster on all attentional tests, yielding statistical significance for the Go/No go test and the Divided Attention test. They also performed with significantly fewer errors on the Divided Attention test. On the Go/No go test, Visual Scanning test and Attentional Shift test ADHD subjects committed significantly more errors than control subjects. CONCLUSIONS: Our results suggest a differential pattern rather than a deficit pattern of attentional functions in ADHD. It is suggested that the more rapid response style of ADHD subjects leads to a more erroneous performance in self-paced attentional tasks and to a better performance in externally paced attentional tasks. However, neuropsychological tests of attention do not contribute to the clinical diagnosis of ADHD.

Command hallucinations: who obeys and who resists when?

The impact of auditory command hallucinations on the behaviour of schizophrenic patients sometimes appears to be unpredictable. In order to tackle this problem, the psychopathological characteristics of command hallucinations in 31 schizophrenic patients were assessed using a 24-item questionnaire. Using binary data and relative risk analysis methods, predictors were determined for obeying or resisting command hallucinations. Characteristics of voices and the attitude toward the voices appear equally important for prediction. A set of three psychopathological characteristics comprising a voice known to the patient, emotional involvement during the hallucinations, and seeing the voice as real provides significant predictivity of behaviour following command hallucinations. These results are interesting for clinical and forensic psychiatrists.

Affect regulation in borderline personality disorder: experimental findings from psychophysiology and functional neuroimaging.

BACKGROUND: Intense and rapidly changing mood states are a major feature of borderline personality disorder (BPD), which is thought to arise from affective vulnerability. OBJECTIVE: There have been only a few studies investigating affective processing in BPD, and particularly neither psychophysiological nor neurofunctional correlates of abnormal emotional processing have been identified so far. METHODS: Studies are reported using psychophysiological or functional neuroimaging methodology. RESULTS: The psychophysiological study did not indicate a general emotional hyperresponsiveness in BPD. Low autonomic arousal seemed to reflect dissociative states in borderline subjects experiencing intense emotions. In the functional magnetic resonance imaging study enhanced amygdala activation was found in BPD, and it is suggested to reflect the intense and slowly subsiding emotions commonly observed in response to even low-level stressors. CONCLUSIONS: Implications for psychotherapy are discussed.

Emotion in criminal offenders with psychopathy and borderline personality disorder.

BACKGROUND: Criminal offenders with a diagnosis of psychopathy or borderline personality disorder (BPD) share an impulsive nature but tend to differ in their style of emotional response. This study aims to use multiple psychophysiologic measures to compare emotional responses to unpleasant and pleasant stimuli. METHODS: Twenty-five psychopaths as defined by the Hare Psychopathy Checklist and 18 subjects with BPD from 2 high-security forensic treatment facilities were included in the study along with 24 control subjects. Electrodermal response was used as an indicator of emotional arousal, modulation of the startle reflex as a measure of valence, and electromyographic activity of the corrugator muscle as an index of emotional expression. RESULTS: Compared with controls, psychopaths were characterized by decreased electrodermal responsiveness, less facial expression, and the absence of affective startle modulation. A higher percentage of psychopaths showed no startle reflex. Subjects with BPD showed a response pattern very similar to that of controls, ie, they showed comparable autonomic arousal, and their startle responses were strongest to unpleasant slides and weakest to pleasant slides. However, corrugator electromyographic activity in subjects with BPD demonstrated little facial modulation when they viewed either pleasant or unpleasant slides. CONCLUSIONS: The results support the theory that psychopaths are characterized by a pronounced lack of fear in response to aversive events. Furthermore, the results suggest a general deficit in processing affective information, regardless of whether stimuli are negative or positive. Emotional hyporesponsiveness was specific to psychopaths, since results for offenders with BPD indicate a widely adequate processing of emotional stimuli.

ICD-10 mild cognitive disorder following meningitis due to neurosarcoidosis.

We report the case of a patient referred to our department with the diagnosis of conversion disorder, who ultimately proved to have neurosarcoidosis presenting with mild cognitive disorder. Despite the criticism of mild cognitive disorder as a diagnostic entity, our patient met the criteria for it. The reported case exemplifies the difficulties in classifying mild cognitive deficits in patients suffering from brain diseases without major morphological damage.

[Posttraumatic stress disorder in patients with neurogenic amnesia for the traumatic event]. / Posttraumatische Belastungsstorung bei neurogener Amnesie fur das traumatische Ereignis.

The development of symptoms of posttraumatic stress disorder (PTSD) in patients with neurogenic amnesia for the traumatic event is recorded in 2 own patients and in 19 cases from the clinical literature. With a single exception, all patients were accident victims with closed head injuries. Only about three quarters of the patients completely fulfilled DSM-III-R criteria of PTSD. Nineteen patients displayed involuntary conscious memories of aspects of the traumatic event (presenting as recurrent intrusive thoughts, images or dreams) co-existent with a complete or partial lack of voluntary conscious memories of the trauma, suggesting that different memory systems and distinct brain mechanisms subserve these phenomena. The said clinical observations are discussed against the background of current neuropsychological models of multiple memory systems. The recorded cases demonstrate that declarative episodic memory is not necessary for symptoms of PTSD to emerge, whereas preserved functions of non-declarative memory systems represent a sufficient condition for the development of PTSD symptoms.

[Impulse control and affect regulation in personality disorders]. / Impulskontrolle und Affektregulation bei Persönlichkeitsstörungen.

In borderline and antisocial personality disorder there is a close interaction between affect dysregulation and impulse control disorder. Different approaches are presented that focus on affective responses to experimental stimuli in these personality disorders. Results suggest that in borderline personality disorder intense emotional responses occur in the context of specific stressors, in particular fear of being abandoned. Evidence for a general emotional hyperreactivity was not found; on the contrary, female borderline subjects rather showed reduced emotional arousal. Regarding the psychopathic subtype of antisocial personality disorder, results provided strong support for the theory of emotional detachment, which may predispose to violence through a lack of feeling of fear or also of compassion which could counteract violent impulses. Consequences for psychotherapy in BPD are considered.

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA)

OBJECTIVES: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic effects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users. METHODS: A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. RESULTS: Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users. CONCLUSIONS: The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are sufficient to cause neurotoxicity in humans.

Emotional responses in patients with borderline as compared with avoidant personality disorder.

The aim of this study was to assess psychophysiological affect correlates, in addition to the usual self-report in borderline personality disorder (BPD) compared with avoidant personality disorder (APD) and normal controls (NCs), when responding to standardized experimental stimuli. In 24 BPD female patients, 23 APD female patients, and 27 female NCs, skin conductance response (SCR), heart rate (HR) change, and startle response were recorded while the subjects viewed slides with emotional content. Neither the self-report nor the psychophysiological data supported the hypothesis that affective responses of BPD individuals are generally stronger than those with APD. BPD patients showed no potentiation of the affective modulation of the startle reflex and their electrodermal reactivity was lower than in either the APD subjects or the NCs. The hypothesis of a general affective hyperresponsivity could not be confirmed. Low somatic arousal in BPD can interfere with the anticipation of signal stimuli and may explain the exaggerated openness borderline personalities show to stimuli, particularly in interpersonal situations.

Comparative sequencing of the human CB1 cannabinoid receptor gene coding exon: no structural mutations in individuals exhibiting extreme responses to cannabis.

Rare but striking individual differences in responsiveness to cannabinoids have been observed that might involve mutations in the gene encoding the brain-expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid receptor coding region was comparatively sequenced in different groups of individuals: one group showed acute psychotic symptoms after cannabis intake, while another group did not develop any psychopathology after long-term heavy cannabis abuse. No evidence for structural mutations was obtained, which might provide some insight into the molecular basis of individually different responsiveness to cannabinoids. Comparison of CB1 cannabinoid receptor amino acid sequences between species substantiated evidence that the protein sequence is relatively well conserved.

Interdisciplinary clinical assessment of patients with illness attributed to environmental factors.

Patients with health problems attributed to environmental factors such as chemical pollutants and electromagnetic fields often do not present evidence of an environmental aetiology of their symptoms. It has been postulated, that their problems are due to disorders diagnosed by other medical disciplines, especially allergology and psychiatry. Our study was designed to subject these patients to a comprehensive diagnostic program involving several medical disciplines in order to achieve diagnoses appropriate to explain the patients' symptoms. Fifty patients consecutively referred to the department of environmental medicine in the university hospital of Aachen, Germany, were submitted to the following examinations: (i) environmental medicine (history, clinical examination, biological and/or ambient monitoring for environmental agents); (ii) allergological examination (history, clinical examination, skin tests); (iii) psychiatric examination (psychopathological examination, psychometric and neuropsychological testing). In addition, the patients were examined in other hospital departments according to the symptoms presented. The findings were discussed in case conferences attended by the physicians involved in order to achieve individual diagnoses. The numbers of patients to whom diagnoses were given by different medical disciplines are as follows: psychiatry (32 patients), dermatology (4), allergology (2), neurology (2), rheumatology (2), gynaecology (1), haematology (1). The most frequent mental disorders diagnosed by the psychiatrists were somatoform disorders (19), followed by schizophreniform and delusion disorders (7). In spite of extensive diagnostic efforts, patients with health problems attributed to the environment usually do not present sufficient evidence of an environmental aetiology of their symptoms. On the other hand the symptoms often meet the diagnostic criteria of other diseases, especially of mental disorders.

Affective responsiveness in borderline personality disorder: a psychophysiological approach.

OBJECTIVE: The aim of the study was to investigate affective responses to emotional stimuli in subjects with borderline personality disorder. METHOD: Twenty-four female patients with borderline personality disorder and 27 normal female comparison subjects were examined. The test stimuli were a set of standardized photographic slides with pleasant, neutral, or unpleasant emotional valence. In addition to self-reports, emotional reactions to the slides were measured by heart rate, skin conductance, and startle response. Psychometric tests for various aspects of impulsiveness were also completed. RESULTS: Neither self-report nor physiological data gave any evidence that the borderline patients showed more intense affective responses than did the normal subjects. The borderline subjects did not produce higher levels of startle amplitude, and while viewing unpleasant slides, they showed a startle potentiation effect that was largely similar to that of the comparison group. In fact, the borderline patients showed low electrodermal responses to all three stimulus categories, which points to physiological underarousal. CONCLUSIONS: The results do not agree with the hypothesis that there is a fundamental, biologically based affective hyperresponsiveness in borderline personality disorder, as is suggested by current theories of affect dysregulation in the disorder. Autonomic underarousal may seriously interfere with a flexible adaptation to environmental stimuli.