Array-CGH and clinical characterization in a patient with subtelomeric 6p deletion without ocular dysgenesis.

Subtelomeric terminal 6p deletion has been recognized as a clinically identifiable syndrome including facial dysmorphism, malformation of the anterior eye chamber, hearing loss, heart defects, and developmental delay. Genotype-phenotype correlations of previously published patients have strongly suggested anterior eye segment anomalies as one of the major malformations of the syndrome if the critical 6p25 region contains the FOXC 1 gene. In addition, the presence in this region of one or more genes involved in hearing loss has been hypothesized. We report a patient with a 47,XYY karyotype and submicroscopic terminal 6p deletion. Further characterization of the deletion with array comparative genome hybridization also revealed a cryptic microduplication on chromosome 19. The patient showed dysmorphic features, neuromotor retardation, and profound language impairment, in absence of hearing loss and structural eye anomalies. As far as we know this is the first reported terminal 6p25.1 deletion case without eye dysgenesis precisely characterized by array-CGH. Our result suggests that the genes in this region may not be obvious candidates for hearing loss and demonstrate the need for further elucidation of the function of the genes involved in eye developmental processes.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

Italian Multicentre Study on Dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease.

For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress.

In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and [76Br]bromospiperone.

The brain regional distribution and kinetics of [76Br]bromospiperone, a derivative of a neuroleptic (spiperone) labeled with the positron emitter bromine-76, were studied by time-of-flight tomography after i.v. injection in man. In a control subject the kinetic distribution study showed an accumulation of radioactivity which reached a maximum 3 h postinjection in the frontal cortex and cerebellum regions and 4-5 h postinjection in the basal ganglia. Thereafter the striatal activity remained essentially constant over a period of 25 h. In a group of 13 control subjects, the mean value for the striatum-to-cerebellum ratio, at 4.5 h postinjection, was 1.84 (S.D. 0.21). In two schizophrenics treated with high doses of haloperidol, this ratio was found to be only 1.22. These data indicate that radiolabeled bromospiperone is very suitable for human pharmacological or pathological investigations of the central dopaminergic system.

Remote effects of caudate hemorrhage: a clinical and functional study.

Clinical, anatomical and functional findings in two cases of previous caudate nucleus hemorrhage, with good recovery, are presented. CBF data obtained with SPECT and 123 I-HIPDM well correlate with functional residual deficit, despite normal TCT examinations. These observations are suggestive of a partial "wallerian" diaschisis.

[Cortical hypometabolism after a thalamic lesion in man: positron tomography study]. / Hypométabolisme cortical après lésion thalamique chez l'homme: étude par la tomographie a positons.

We used positron emission tomography to study the effects of unilateral vascular thalamic lesions on cortical oxygen or glucose utilisation in 10 patients. There was a significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting diffusely the whole cortical mantle. The only patient spared was free of neuropsychological deficit at time of PET study. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at follow-up PET study, together with improved neuropsychological function. When plotted altogether, the 14 studies showed a significant tendency for the hypometabolism to improve with time elapsed since clinical onset. On the whole, these data suggest that the ipsilateral cortical hypometabolism reflects an essentially functional alteration an not only a degenerating process. This most likely indicates a cortical deafferentation due to loss of non-specific thalamo-cortical connections, i.e. a phenomenon akin to "diaschisis". However, a causal relationship between cortical hypometabolism and neuropsychological deficit cannot be firmly established from the present data.

[Clinical experience with imipenem-cilastatin in intensive therapy]. / Esperienza clinica con imipenem-cilastatina in terapia intensiva.

The authors describe their experience with imipenem-cilastatin in 36 patients in critical conditions due to multiresistant bacterial infections. The efficacy and tolerability of the antibiotic are stressed.

Serum lipoprotein pattern variations in dementia and ischemic stroke.

Blood levels of triglycerides, total cholesterol, isolated lipoprotein fractions (VLDL-LDL- and HDL-cholesterol) and apoproteins (Apo-A1 and Apo-B) were examined in multi-infarct dementia, senile dementia of the Alzheimer type, ischemic stroke associated with carotid atherosclerosis and in control subjects. Forty patients divided into 10 consecutive patients for each group were studied. Alzheimer patients showed mean total cholesterol and Apo-B values significantly higher than control subjects. Apo-B was significantly higher in stroke patients than in controls. The mean lowest HDL-cholesterol (HDL-c) value was observed in stroke patients. No significant differences in mean HDL-c levels were found between patients with multi-infarct and Alzheimer dementia.

Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy.

The dementia associated with progressive supranuclear palsy (PSP) is considered to be subcortical because the cerebral cortex, unlike the subcortical structures, is usually free from major neuropathological lesions; the characteristic symptoms point to a dysfunction of the prefrontal lobe. The regional cerebral metabolic rate of glucose (rCMR Glu) was studied by positron emission tomography and 18F-fluoro-2-deoxyglucose18FDG in 6 patients presumed to have PSP and was compared with values found in 8 control subjects of similar age. The results obtained showed a highly significant rCMR Glu decrease in the prefrontal cortex of our patients. The loss of several subcortical afferents to prefrontal cortex may be responsible for the frontal cortical hypometabolism present in PSP.

Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man.

Positron emission tomography was used to study the effects of unilateral vascular thalamic lesions on cortical oxygen and glucose utilization in 10 patients. There was significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting the whole cortical mantle diffusely. The only patient spared was free of neuropsychological deficit at the time of positron emission tomography. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at a follow-up PET study, when neuropsychological function had improved. When taken together, the 14 studies showed a significant tendency for the hypometabolism to improve with time after clinical onset. These data suggest that the ipsilateral cortical hypometabolism results from damage to the thalamocortical connections and reflect either loss of nonspecific activating afferences or a degenerative deafferentation-deafferentation process, or both. Its links with the concept of diaschisis are suggested by its tendency to recover. A causal relationship between cortical hypometabolism and neuropsychological deficit, however, although strongly suggested, cannot be firmly established from the present data.