Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis.

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF may negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover

Italian standardization of the Apples Cancellation Test

Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, resulting in poor functional gain. Recent research has shown that different types of neglect can impact in a different way on rehabilitation outcomes. The availability of a sensitive test, useful for distinguishing egocentric and allocentric forms of neglect, may be clinically important as all current clinical instruments fail to distinguish between these forms of disturbance, yet they differentially predict outcome. The Apples Test is a new instrument useful to evaluate both egocentric and allocentric forms of neglect. In order to establish Italian norms for this diagnostic instrument the test was administered to a sample of 412 healthy people of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14 different rehabilitation centers in Italy. Based on the data, we established pathological performance cut-offs for the accuracy score (total omission errors), the asymmetry score for egocentric neglect (omission error difference), the asymmetry score for allocentric neglect (commission error difference) and execution time. The usefulness of the Apples Test for diagnostic purposes is illustrated by presenting three patients with different forms of neglect (egocentric, allocentric and mixed neglect)

Effect of a medical food on body mass index and activities of daily living in patients with Alzheimer's disease: secondary analyses from a randomized, controlled trial

Contains fulltext : 97852.pdf (publisher's version ) (Closed access)OBJECTIVES: To investigate the effect of a medical food (Souvenaid) on body mass index (BMI) and functional abilities in patients with mild Alzheimer's disease (AD). DESIGN/SETTING/PARTICIPANTS/INTERVENTION /MEASUREMENTS: These analyses were performed on data from a 12-week, double-blind, randomized, controlled, multicenter, proof-of-concept study with a similarly designed and exploratory 12-week extension period. Patients with mild AD (Mini-Mental State Examination score of 20-26) were randomized to receive either the active product or an iso-caloric control product. While primary outcomes included measures of cognition, the 23-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale was included as a secondary outcome. Both ADCS-ADL and BMI were assessed at baseline and Weeks 6, 12 and 24. Data were analyzed using a repeated-measures mixed model. RESULTS: Overall, data suggested an increased BMI in the active versus the control group at Week 24 (ITT: p = 0.07; PP: p = 0.03), but no treatment effect on ADCS-ADL was observed. However, baseline BMI was found to be a significant treatment effect modifier (ITT: p = 0.04; PP: p = 0.05), and an increase in ADCS-ADL was observed at Week 12 in patients with a 'low' baseline BMI (ITT: p = 0.02; PP: p = 0.04). CONCLUSIONS: These data indicate that baseline BMI significantly impacts the effect of Souvenaid on functional abilities. In addition, there was a suggestion that Souvenaid increased BMI

A case of atypical progressive supranuclear palsy

Simona Spaccavento, Marina Del Prete, Angela Craca, Anna Loverre IRCCS Salvatore Maugeri Foundation, Cassano Murge, Bari, Italy Background: Progressive supranuclear palsy (PSP) is a neurodegenerative extrapyramidal syndrome. Studies have demonstrated that PSP can present clinically as an atypical dementing syndrome dominated by a progressive apraxia of speech (AOS) and aphasia. Aim: We aimed to investigate the clinical presentation of PSP, using a comprehensive multidimensional evaluation, and the disease response to various pharmacological treatments. Methods: A 72-year-old right-handed male, with 17 years education, who first presented with aphasia, AOS, depression, apathy, and postural instability at 69 years; a complete neuropsychological evaluation, tapping the different cognitive domains, was performed. Results: Testing revealed a moderate global cognitive deficit (Mini-Mental State Examination test score =20), low memory test scores (story recall, Rey’s 15-word Immediate and Delayed Recall), and poor phonemic and semantic fluency. The patient’s language was characterized by AOS, with slow speech rate, prolonged intervals between syllables and words, decreased articulatory accuracy, sound distortions, and anomia. Behavioral changes, such as depression, anxiety, apathy, and irritability, were reported. The neurological examination revealed supranuclear vertical gaze palsy, poor face miming, and a mild balance deficit. Magnetic resonance imaging showed only widespread cortical atrophy. Single photon emission computed tomography demonstrated left > right frontotemporal cortical abnormalities. After 6 months, a further neuropsychological assessment showed a progression in cognitive deficits, with additional attention deficits. The patient reported frequent falls, but the neurological deficits remained unchanged. Neuroimaging tests showed the same brain involvement. Conclusion: Our case highlights the heterogeneity of the clinical features in this syndrome, demonstrating that atypical PSP can present as AOS and aphasia, without the classical features or involvement of the subcortical gray and brainstem region, commonly affected in typical PSP. Keywords: pharmacological treatments, neuropsychological deficit

Different Cognitive Profiles of Patients with severe aphasia

Cognitive dysfunction frequently occurs in aphasic patients and primarily compromises linguistic skills: patients suffering from severe aphasia show heterogeneous performance in basic cognition. Our aim was to characterize the cognitive profiles of patients with severe aphasia and to determine whether they also differ as to residual linguistic abilities. We examined 189 patients with severe aphasia with standard language tests and with the CoBaGA (Cognitive Test Battery for Global Aphasia), a battery of non-verbal tests that assesses a wide range of cognitive domains such as attention, executive functions and intelligence and memory, visual/auditory recognition and visual-spatial abilities. We also examined 20 patients longitudinally to assess their improvement in cognitive skills after speech therapy. Three different sub-groups of patients with different types and severity of cognitive impairment were evidenced. Sub-groups differed as to residual linguistic skills, in particular comprehension and reading-writing abilities. Attention and reasoning/executive function improved after language rehabilitation. This study highlights the importance of an extensive evaluation of cognitive functions in patients with severe aphasia