Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract.

The synthesis of ferritin, the iron-storing molecule, is regulated at the translational level by iron through interaction between a cytoplasmic protein, iron regulatory protein (IRP), and a conserved nucleotide motif present in the 5' non-coding region of all ferritin mRNAs--the iron responsive element (IRE). This region forms a stem-loop structure and when the supply of iron to the cells is limited, the IRP is bound to IRE and represses ferritin synthesis. Ferritin is composed of a 24-subunit protein shell surrounding an iron core. The two types of subunit, H and L, are encoded by two genes located on chromosomes 11q13 and 19q13.1, respectively. Both genes are ubiquitously expressed but transcriptional regulation mediates tissue-specific changes in the H/L mRNA ratio and isoferritin profiles. We now report the identification of a single point mutation in the IRE of the L-ferritin mRNA in members from a family affected with dominantly inherited hyperferritinaemia and cataract. This mutation consists of an A to G change in the highly conserved CAGUGU motif that constitutes the IRE loop and mediates the high-affinity interaction with the IRP. We show that this mutation abolishes the binding of IRP in vitro and leads to a high constitutive, poorly regulated L-ferritin synthesis in cultured lymphoblastoid cells established from affected patients. This is, to our knowledge, the first mutation affecting the IRP-IRE interaction and the iron-mediated regulation of ferritin synthesis. We suggest that excess production of ferritin in tissues is responsible for the hyperferritinaemia and that intracellular accumulation of ferritin leads to cataract.

Geometry of color perception. Part 2: perceived colors from real quantum states and Hering's rebit.

Inspired by the pioneer work of H.L. Resnikoff, which is described in full detail in the first part of this two-part paper, we give a quantum description of the space [Formula: see text] of perceived colors. We show that [Formula: see text] is the effect space of a rebit, a real quantum qubit, whose state space is isometric to Klein's hyperbolic disk. This chromatic state space of perceived colors can be represented as a Bloch disk of real dimension 2 that coincides with Hering's disk given by the color opponency mechanism. Attributes of perceived colors, hue and saturation, are defined in terms of Von Neumann entropy.

Early occupational therapy programme increases hand grip strength at 3 months: results from a randomised, blind, controlled study in early rheumatoid arthritis.

AIM: The goal of occupational therapy (OT) is to facilitate adjustments to lifestyle and to prevent function loss. This study evaluated the effects of an early OT programme in early rheumatoid arthritis (RA). METHODS: We conducted a randomised, blind, controlled trial enrolling 60 patients with early RA, divided into 2 groups. At baseline, group 1 received the full information programme and group 2 received no information. In an extension phase, patients in group 2 received the full information programme at 3 months and were assessed at 6 months. The main outcomes were grip strength of hands (as objective assessment) and Health Assessment Questionnaire (HAQ) score (as subjective assessment). RESULTS: At 3 months, grip strength of the dominant and non-dominant hands increased more in group 1 than in group 2 (p = 0.021 and 0.047 respectively). HAQ score decreased more in group 1 than in group 2 (p<0.001). In the extension phase, changes in grip strength and HAQ score in group 2 were similar to those seen in group 1 between baseline and 3 months. CONCLUSIONS: This study comparing two schedules of OT programme showed that an early extended information programme improved hand function in patients with early RA.

Quantitative and qualitative hydrologic balance for a suburban watershed with a separate sewer system (Nantes, France).

A qualitative and quantitative budget at the outlet of the storm-water runoff system of a small suburban watershed is presented together with some data regarding waste-water. 445,000 m3 (34% of the rain-water volume) were drained by the storm-water runoff system and 40,879 m3 by the waste-water system from September 2002 to March 2004. Storm-water runoff is generally not heavily polluted with regard to trace metals but concentrations occasionally exceed the standards for surface water of good quality. On the contrary, pesticides (diuron and glyphosate) have very high concentrations especially in spring and autumn when their use is maximum. As the St Joseph storm-water runoff is finally discharged into the Erdre River, measures to reduce the use of these pollutants should be considered.

Bipolar disorder in adult patients with Tourette's syndrome: a clinical study.

BACKGROUND: Although recent clinical and epidemiological studies indicate that Tourette's syndrome (TS) is associated with a higher than expected rate of bipolar disorder (BPD), the clinical characteristics of BPD in patients with TS have not been widely investigated. METHODS: Thirty adult TS patients with comorbid BPD were selected from a consecutive series of 90 referred TS patients and examined using structured psychiatric rating scales. RESULTS: The full clinical spectrum of BPD was found, including bipolar I disorder, schizoaffective bipolar disorder, bipolar II disorder, and cyclothymic disorder. Atypical vegetative depressive symptoms, rapid cycling patterns, and seasonal patterns of recurrence were also documented. In the present clinical sample, BPD mainly occurred in patients with mild tic symptoms and was invariably associated with a high lifetime prevalence of general psychopathology, including generalized anxiety disorder, obsessive-compulsive disorder, panic, phobias, eating disorders, self-injurious behavior, attention-deficit hyperactivity disorder, impulse control disorders, and personality disorders. CONCLUSIONS: The results of this clinical study indicate that BPD and nonaffective psychopathology may be prominent comorbid disorders in a subpopulation of patients with TS.

Manic-depressive and pure manic states after brain lesions.

Although mania is a rare complication of brain lesions, recent reports have emphasized the importance of lesion location and genetic predisposition in these patients. In the present study we compared patients who developed a bipolar affective disorder (i.e., mania and depression) after a brain lesion with patients who only developed mania. Although no significant between-group differences were found on demographic variables, the manic-depressed group showed significantly more impairments on the Mini Mental State Exam than the mania only group. All the bipolar patients had subcortical lesions (mainly right head of the caudate and right thalamus), while patients with unipolar mania had significantly higher frequency of cortical involvement (mainly right orbitofrontal and basotemporal cortices). It is suggested that subcortical and cortical right hemisphere lesions may produce different neurochemical and/or remote metabolic brain changes that may underlie the production of either a bipolar disease or a unipolar mania.

REM sleep latency and contingent negative variation in endogenous depression. Suggestion for a common cholinergic mechanism.

In a sample of 13 endogenous depressive inpatients, REM (rapid eye movement) latency (recorded over 4 consecutive nights after 2 habituation nights) and contingent negative variation amplitude showed significant relationship, suggesting that both parameters may depend on the same mechanisms, possibly cholinergic.

Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism.

Magnetic resonance imaging (MRI) scans were performed on 13 high-functioning male autistic subjects and 13 male nonautistic control subjects comparable in age and nonverbal IQ. Scans were rated for the presence of cerebral cortical malformations. Five autistic subjects had polymicrogyria, one had schizencephaly and macrogyria, and one had macrogyria. None of the control subjects had abnormalities of this type. These abnormalities result from a defect in the migration of neurons to the cerebral cortex during the first 6 months of gestation. The detection of these malformations by MRI, their pathogenesis, and the implications regarding the pathogenesis of autism are discussed.

Differential mood changes following basal ganglia vs thalamic lesions.

Patients with computed tomographic scan-verified unilateral lesions in the basal ganglia or thalamus were examined for the presence of poststroke mood disorders. Patients with left-sided basal ganglia lesions (mainly in the head of the caudate nucleus) showed a significantly higher frequency and severity of depression, as compared with patients with right-sided basal ganglia or thalamic (left- or right-sided) lesions. Results suggest that damage to biogenic amine pathways and/or frontocaudate projections may play an important role in the modulation of mood.

Unrecognized Tourette syndrome in adult patients referred for psychogenic tremor.

BACKGROUND: The diagnosis of Tourette syndrome may be overlooked in patients with severe psychopathologic disorder but mild motor manifestations of Tourette syndrome. OBJECTIVE: To describe 4 patients with long-lasting general psychopathologic disorder and previously unrecognized mild motor and phonic tics exacerbated during adulthood by the onset of tremor; all of the patients had been referred for the evaluation of psychogenic tremor. SUBJECTS: Four adult patients, with previous psychiatric diagnoses of depression (2 cases), generalized anxiety disorder (3 cases), malingering (1 case), and conversion disorder (3 cases). METHODS: Single case studies. RESULTS: Clinical interviews disclosed that the 4 patients had positive family histories of Tourette syndrome, and all had mild motor and phonic tics that had started before the age of 18 years. On neurologic examination, 2 patients had bilateral postural tremor of the hands that varied in frequency, rhythmicity, and amplitude, and the other 2 had resting tremor mimicking parkinsonism. All 4 patients described involuntary somatic sensations of the affected limbs, which they attempted to alleviate by executing movements. No consistent positive placebo response was observed, but in all patients tremoric movements improved with haloperidol. CONCLUSIONS: These cases illustrate an unusual movement disorder (tremor as a "tic equivalent") in adults with Tourette syndrome and emphasize that cases of the syndrome with mild tics often go unrecognized, precluding adequate treatment.

Neuropsychological disturbances in hemiparkinson's disease.

Nine parkinsonian patients with main unilateral symptoms on the right side (RHP) and nine with symptoms on the left side (LHP) were assessed through a comprehensive neuropsychological battery. RHP performed at a lower level than LHP on the WAIS verbal subtests. Although both groups scored poorly on a test of frontal lobe functions, RHP performed significantly lower than LHP. On a line bisection task, LHP showed a mild left hemispatial neglect. In conclusion, mild but significant intergroup differences were observed, tending to correlate with predominantly hemispheric functional deficits.

Hemiballismus and secondary mania following a right thalamic infarction.

An 81-year-old woman had the sudden onset of left-sided ballismus and an accompanying behavioral change characterized by elation, distractibility, inflated self-esteem, and insomnia, suggesting secondary mania. An MRI revealed a small ischemic infarction of the right thalamus.

Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates.

We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age at onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD.

Anosognosia and major depression in 2 patients with cerebrovascular lesions.

We report 2 patients who developed a neglect syndrome, anosognosia, and major depression immediately after a right hemisphere cerebrovascular lesion. These cases demonstrate that neglect, anosognosia, and major depression may coexist in the same patient, and that the presence of anosognosia does not preclude the patient's recognition of emotional impairment.

Acute CNS infection by Trypanosoma cruzi (Chagas' disease) in immunosuppressed patients.

Acute CNS involvement by Trypanosoma cruzi is uncommon. We report 2 immunosuppressed patients, 1 adult who developed an acute meningoencephalitis, and 1 child who presented with the tumor-like form of the disease. Both patients acquired the disease through blood transfusion. Blood donors migrating from endemic areas can transmit the disease in nonendemic countries if they are not routinely screened for antibodies to T cruzi.

Depression in patients with early versus late onset of Parkinson's disease.

We examined correlates of depression in patients whose onset of Parkinson's disease (PD) began before age 55 (early-onset group) compared with patients whose onset was after age 55 (late-onset group). The early-onset group showed a significantly higher frequency of depression than the late-onset group. When both groups were matched for duration of the disease, the early-onset group still showed a significantly higher frequency of depression, whereas tremor, akinesia, and rigidity were significantly more severe in the late-onset group. A stepwise regression analysis showed that in the early-onset group, depression scores were significantly correlated with scores of cognitive impairment and duration of the disease, while in the late-onset group, depression scores were significantly correlated with impairments in activities of daily living. These data suggest that depression in patients with early-onset PD may have a different etiology than in patients with late-onset PD.

Mania following deep brain stimulation for Parkinson's disease.

Three patients with PD developed manic behavior after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common to all three patients were manic symptoms unremitting after levodopa reduction or stimulation "off," lower electrodes positioning caudal to the subthalamic nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar electrodes, and resolution of the manic episodes coinciding with stimulation through higher contacts.

Intensity dependence of auditory evoked potentials is pronounced in migraine: an indication of cortical potentiation and low serotonergic neurotransmission?

Migraine is associated with stimulus hypersensitivity, increased evoked cortical responses, and abnormal 5-HT levels in peripheral blood. We studied cortical auditory evoked potentials (AEPs) between attacks in 35 patients suffering from migraine without aura (MO, n = 25) or with aura (MA, n = 10) and in 25 healthy volunteers. Binaural tones were delivered at 40, 50, 60, and 70 dB sensation level (SL) in a pseudorandomized order. The intensity dependence of the auditory N1-P2 component was significantly greater in MO (p = 0.003) and MA (p = 0.02) patients than in healthy controls, resulting in a much steeper amplitude/stimulus intensity function slope. When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities, N1-P2 amplitude decreased in second and third blocks at both intensities in controls, but increased in migraineurs, a difference that was significant in both blocks for the 70-dB SL stimulus. The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation (instead of habituation) of the response during repetition of the high-intensity stimulation. In concordance with previous studies of visual evoked potentials, these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing, which might be a consequence of low 5-HT transmission and favor cortical energy demands.

Effects of repetitive transcranial magnetic stimulation on memory subtypes: a controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.

Inhibitory influence of oxytocin infusion on contingent negative variation and some memory tasks in normal men.

A double-blind study combining electrophysiological and psychometrical approaches was carried out to investigate the central effects of an intravenous oxytocin (OT) infusion in normal men. Contingent negative variation (CNV) was selected as the measure of central cognitive evoked potential, and the psychometric tests measured mood, vigilance and memory. OT infusion induced a significant decrease of CNV amplitude and an increase of post-imperative positive potentials in vertex derivations. A similar effect was still evidenced one week after treatment in frontal derivations, suggesting a long time effect of OT on human brain. No significant influence of OT on mood or vigilance tests was apparent; only one item of a memory test revealed a significant impairment of some mnesic performances. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man.