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Biomedical subjects

A Mauro

Publications and source records attributed to A Mauro.

At least 19 recordsLinked to original sources

Visual hallucinations in Parkinson's disease: clues to separate origins.

Our paper discusses two experimental studies suggesting that Visual Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The first is a prospective 8years study evaluating the appearance of VH, visual abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA). In chronically treated, cognitively unimpaired, PD patients VH were statistically related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were significantly reduced by l-Dopa or DA intake, and were statistically unrelated to VH. The second study involved PD patients placed in a Virtual Reality Environment, to decontextualize visual input. When motor symptoms worsened and VEP abnormalities developed patients consistently described hallucinatory dysperceptions of the virtual environment. The two studies therefore show that VH can occur in two seemingly distinct conditions, one is related to chronic treatment and to a sleep disorder frequently observed in PD, the other is probably related to a hypodopaminergic state. Our studies support a recently proposed integrative model of VH, and show that the neural circuits purported to explain VH must include the retinal dopaminergic system and the REM sleep regulatory system.

Antiparkinson Agents↗

Depression is the main determinant of quality of life in multiple sclerosis: a classification-regression (CART) study.

PURPOSE: Quality of life in multiple sclerosis has been often measured through the SF-36 questionnaire. In this study, validation of the SF-36 summary scores, its 'physical' component, and its 'mental' component was attempted by exploring the joint predictive power of disability (EDSS score), of anxiety and depression (HADS-A and -D scores, respectively), and of disease duration, progression type, age, gender and marital status. METHOD: The sample consisted of 75 patients suffering from multiple sclerosis admitted to an inpatient rehabilitation unit. The interplay between potential predictors was assessed through a particular regression model (classification and regression tree, CART). Two main advantages of this technique are its robustness with respect to distributional assumptions (rarely met by scores coming in from questionnaires) and its sensitivity to high-order interactions, between independent variables, difficult to detect through conventional multiple regression. RESULTS: Predictive variables for physical component of the SF-36 were EDSS and HADS-D (36.8% variance explanation). The only predictive variable for mental component of SF-36 was HADS-D (39.1% variance explanation). CONCLUSION: Results confirm previous findings showing that in patients with multiple sclerosis quality of life is heavily determined by person's mood, whatever his/her neurological or functional severity. The usefulness and validity of the SF-36 as an index representative of quality of life is debatable, as long as depression explains much of its variance. Further refinement of quality of life definition and measurement is worth further psychometric and statistical research.

Adult↗

Decision-making in obesity: a study using the Gambling Task.

The present study addresses the issue of whether a "decision-making disorder" could account for the behavioral problems of severely obese patients (BMI score >34) who are not classified by traditional psychiatric Eating Disorder tests. The neuropsychological test employed, the Gambling Task (GT), is not directly related to the food domain, but it is sensitive to failure in making long-term advantageous choices. A comparison was made of 20 obese subjects (OS) and 20 normal-weight subjects (NWS) matched in age, education and IQ. The subjects' personalities and food behavior were assessed from psychological questionnaires, and then the Gambling Task was administered. The number of "good" choices made by the two groups during GT performance differed significantly, and the OS did not learn to maximize advantageous choices like the NWS did. OS behavior could be consistent with a prefrontal cortex defect that implies difficulties in inhibition of excessive food intake.

Adult↗

Spatio-temporal analysis of vascular endothelial growth factor expression and blood vessel remodelling in pig ovarian follicles during the periovulatory period.

Vascular endothelial growth factor (VEGF) expression pattern and blood vessel remodelling were evaluated during the transition from the preovulatory follicle to the corpus luteum (CL). To this end, prepubertal gilts were treated with equine chorionic gonadotrophin (eCG) to collect preovulatory follicles (60 h after eCG) and with human chorionic gonadotrophin (hCG) to obtain periovulatory follicles 18 h and 36 h later. The VEGF mRNA content was analysed by in situ hybridization, while protein localization in follicular fluid (FF) and in granulosa and theca compartments was evaluated by ELISA, immunohistochemistry or western blot. Blood vessel architecture and vascular area (VA) were investigated using immunohistochemistry for von Willenbrand Factor, a specific endothelial marker. Vascular remodelling was finally tested using Ki-67 immunocytochemistry as a proliferation marker, or alpha-smooth muscle actin (alpha-SMA) as a specific mural cell marker. eCG-treated follicles showed high VEGF levels and two concentric blood vessel networks composed of proliferating endothelial cells without any association with mural components. hCG injection inhibited VEGF synthesis in the granulosa compartment and, as a consequence, the protein fell within the FF. In parallel, endothelial cell proliferation stopped and the VA decreased. Close to ovulation, VEGF production restarted in both follicular compartments and VEGF mRNA content significantly increased in the theca layer. Changes in follicular VEGF secretion were observed; the protein disappeared from FF and was observed in the extracellular matrix. An active angiogenesis characterized the follicle; endothelial cell proliferation was associated with a recruitment of alpha-SMA-positive mural cells. The data presented in this work showed that, in the phases preceding ovulation, a complete vascular remodelling occurs, characterized by both an evident neovascularization and the appearance of blood vessels presenting smooth musculature which could be involved in CL formation after ovulation.

Actins↗

How does stroke restrict participation in long-term post-stroke survivors?

OBJECTIVE: To explore the factors determining 'restricted participation' in a selected population of long-term post-stroke survivors. MATERIALS AND METHODS: Seventy-three consecutive post-stroke inpatients were scored for mood and restriction in participation by means of self-administered questionnaires, respectively the Hospital Anxiety and Depression Scale (HADS/A; HADS/D) and London Handicap Scale (LHS). Neurological impairment and functional disability were evaluated with the Unified Neurological Stroke Scale (UNSS) and Functional Independence Measure (FIM). RESULTS: Physical independence and occupation were the most severely affected domains on the LHS. UNSS, FIM, HADS/A, HADS/D scores were significant determinants of restriction in participation at univariate analysis performed with each LHS domain. FIM score and emotional status finally emerged as the independent determinants of restricted participation for the LHS domains most related to body function (mobility, physical independence, occupation). Depression was the determinant factor for orientation and social integration. CONCLUSION: Functional disability and mood disorders may independently contribute to the restricted participation of post-stroke patients. Most of the LHS domains remain stable over time.

Activities of Daily Living↗

Body composition in advanced-stage Parkinson's disease.

Little is known about body composition in Parkinson's disease (PD). We studied 35 patients (20 male, 15 female subjects; mean age 69.7+/-5.8 years) with advanced PD by anthropometry, dual-energy X-ray absorptiometry (DEXA), and serum 25-OH vitamin D measurement. Over 70% of patients had a disease duration of more than 4 years; all were on L-dopa treatment. Low levels of serum 25-OH vitamin D were present in 41% of the patients. The mean body mass index (BMI) was 25.3+/-4.3 kg/m(2) (range 17.1-37.3). Mid-arm muscle circumference was below the 10th percentile in 23%. For whole-body mean (+/-SD) bone mineral density, the T score was below -1 SD in 35% of patients, and the Z score was below -1 SD in 24%. Percent fat mass measured with DEXA was 30.6+/-11.4% (range 10.1-45.5) in the overall sample; it was 21.1+/-8.8% (range 10.1-30.4) in male subjects and 38.1+/-9.2% (range 25.8-45.5) in female subjects. We conclude that advanced-stage PD may show excess adiposity coexisting with depletion of lean body mass (sarcopenic obesity), in addition to decreased whole-body bone mineral density associated with low serum 25-OH vitamin D. A low level of physical activity and inadequate exposure to sunlight are likely to be among the putative causes.

Absorptiometry, Photon↗

Nocturnal anomalous movement reduction and sleep microstructure analysis in parkinsonian patients during 1-night transdermal apomorphine treatment.

This study analyzed the macrostructure and microstructure of sleep in 12 parkinsonian patients under basal conditions (T0) and during 1-night treatment (T1) with a new formulation of apomorphine. This new formulation consisted in a microemulsion of apomorphine administered by the transdermal route, able to provide a constant release of the drug over several hours (APO-TD). Sleep analysis at T1 compared with T0 revealed a 16% increment of total sleep time, a 12% increment of sleep efficiency, a 16% increment of stage 3 and 4 non-REM sleep, a 15% reduction of periodic limb movements index, a 22% reduction of arousal index, and a 23% reduction of cycling alternating patterns/non-REM. We conclude that APO-TD may be able to reduce nocturnal anomalous movements, akinesia, and rigidity in Parkinson's disease, and may reduce the disturbed sleep typical of Parkinson's disease.

Administration, Cutaneous↗

Are the neurophysiological techniques useful for the diagnosis of diaphragmatic impairment in multiple sclerosis (MS)?

OBJECTIVE: To characterize cortico-diaphragmatic pathway involvement in multiple sclerosis (MS) by means of transcranial magnetic stimulation (TMS), and verify its clinical impact. METHODS: TMS from diaphragm (Dia), and abductor digiti minimi (AbdV degrees ) was performed in 26 MS patients. Phrenic nerve (PN) conduction study was also performed. Expanded disability status scale (EDSS) and fatigue descriptive scale (FDS) were measured. Forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), peak expiratory flow (PEF) were tested: the predicted percentage value (% pred) was considered. RESULTS: Cortical motor evoked potential (Cx-MEP) latency and central motor conduction time (CMCT) were prolonged, respectively, in 31 and 23% of patients from Dia, in 76 and 79% from AbdV degrees. PN-compound motor action potential (CMAP) was normal. EDSS correlated to Cx-MEP from AbdV degrees (P<0.01), and PN-CMAP amplitude (P<0.05), FEV1 % pred (P<0.01), PEF % pred (P<0.01). PN-CMAP amplitude correlated to FVC % pred P=0.05, FEV1 % pred P<0.01, PEF % pred P<0.01. Fatigue was related to AbdV degrees Cx-MEP and CMCT (P<0.05 and P<0.01). CONCLUSIONS: Cortico-diaphragmatic pathway is impaired only in a minority of MS patients. Lack of correlation between TMS findings from Dia and respiratory tests argues against its routinary use to detect subclinical respiratory alterations. Fatigue seems to be related to the motor impairment rather than to respiratory distress.

Adult↗

Common daily activities in the virtual environment: a preliminary study in parkinsonian patients.

Patients with Parkinson's disease (PD) create behavioral motor strategies by using external cues to facilitate their movements. Virtual reality (VR) could work as an external stimulus in order to explore the motor plans by means of creation of mental images. We tested 2 women with PD aged 68 and 69 years, and 10 normal control subjects. Patients underwent a neuropsychological assessment to evaluate cognitive abilities involved in the tasks required by the VR session. VR environment reproduces common daily activities situations at home, such as eating or using the bathroom. VR describes the alterations of the motor plans in PD by a point of view different from the clinical one, by testing "pure" mental sequences of the execution of a movement, without the interference of motor disability.

Activities of Daily Living↗

Controlled-release transdermal apomorphine treatment for motor fluctuations in Parkinson's disease.

This study evaluated the efficacy in Parkinson's disease (PD) of a new pharmacologic preparation of apomorphine included in microemulsions and administered by transdermal route, which provides a constant release of the drug for several hours (Apo-TD). Twenty-one PD patients with motor fluctuations were treated with L-dopa alone, with L-dopa plus oral dopamine-agonists, or with L-dopa plus Apo-TD. Apo-TD improved UPDRS-III and tapping test scores in "off" conditions, and reduced duration of "off" periods; no improvement in "on" conditions occurred. We conclude that Apo-TD shows its efficacy particularly by reducing "off" period duration and disability rather than improving motor performances in "on" conditions and therefore it seems a promising treatment for uncontrolled "off" phases in PD patients.

Administration, Cutaneous↗

The role of language areas in motor control dysfunction in Parkinson's disease.

We evaluated the differences in motor control organization between parkinsonian patients with (seven cases) and without (ten cases) gait disorder. We used positron emission tomography (O15-H2O-PET) to measure regional cerebral blood flow as a correlate for local neuronal activation. This has been assessed during repetitive joystick movements of the right hand, externally triggered using a metronome as an auditory cue. In patients with Parkinson's disease (PD) without gait disorder, the contralateral supplementary motor cortex and the bilateral cerebellum were activated, while in PD patients with gait disorder the contralateral Broca's area, the contralateral sensory motor cortex and the homolateral cerebellum were activated. Our results suggest that PD patients with gait disorder creates an internal verbal cue in order to control the output of the movement of joystick, supplying the loss of control of the supplementary motor cortex that is activated in patients without gait disorder.

Brain↗

CDKN2A/p16 in ependymomas.

Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.

Adolescent↗

Virulence factors in Vibrios and Aeromonads isolated from seafood.

Thirty-one isolates from seafood, identified as Aeromonas hydrophila (7), Aeromonas caviae (11), Vibrio parahaemolyticus (3), Vibrio fluvialis (5), Vibrio alginolytictus (3), Vibrio metschnikovii (1) and Vibrio damsela (1), were tested for possible virulence factors including extracellular hydrolytic enzymes, haemolysins, cytotoxins (VERO and HEp-2 cells) and adherence ability (HEp-2 cells). All the A. hydrophila strains were beta-haemolytic and produced cytotoxins as well as one strain of V. fluvialis. A. hydrophila and A. caviae strains, frequently adhesive, showed both aggregative and diffusive patterns, while five Vibrio strains only (three V. fluvialis, one V. parahaemolyticus and one V. alginolyticus) were adhesive with an aggregative pattern.

Aeromonas↗

CDKN2A/p16 inactivation in the prognosis of oligodendrogliomas.

The cell-cycle regulator p16 inhibits the complex cdk4-cyclin D1 and controls G1-S transition. In human tumors, p16 inactivation is often accomplished by homozygous deletion (HD) of its encoding gene, CDKN2A. Methylation of the 5' CpG island promoter has been proposed as an alternative mechanism of inactivation. Expression of p16, CDKN2A HD and 5' CDKN2A CpG island methylation was studied in 25 oligodendrogliomas by immunohistochemistry and PCR amplification. Ten oligodendrogliomas were p16-immunonegative, and CDKN2A HD was determined in 8 of these cases. In the 2 immunonegative cases without HD, no CpG island methylation was found. The absence of CpG island methylation in the p16-immunonegative cases without HD suggests either non-genetic regulation of p16 or different genetic changes. CDKN2A HD did not correlate with histological grading (p = n.s.); however, it showed a correlation with survival (p = 0.03), supporting an important role of CDKN2A in the prognosis of oligodendrogliomas.

Brain Neoplasms↗

An Italian family with Ala-47 transthyretin mutation associated with cardiomyopathy and polyneuropathy.

We describe two Italian first cousins with familial amyloidotic polyneuropathy associated with transthyretin variant consisting of the substitution of alanine for glycine at codon 47 (TTR Ala-47), from a family with a history of cardiac failure. The 40-year-old patient presented with autonomic dysfunction and the 44-year-old cousin with congestive heart failure. Both developed sensorimotor and autonomic polyneuropathy. Since a similar clinical picture has been described in another Italian family, the cardiac involvement must be regarded as a salient and early feature of the TTR Ala-47 mutation.

Adult↗

Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats.

Both chronic hyperglycemia and ischemia/reperfusion (IR) cause an imbalance in the oxidative state of tissues. Normoglycemic and streptozotocin (STZ)-diabetic rats were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 60 min. Rats had either been treated with dehydroepiandrosterone (DHEA) for 7, 14, or 21 days (2 or 4 mg/day per rat) or left untreated. Oxidative state, antioxidant balance, and membrane integrity were evaluated in isolated synaptosomes. IR increased the levels of reactive species and worsened the synaptic function, affecting membrane Na/K-ATPase activity and lactate dehydrogenase release in all rats. The oxidative imbalance was much severer when transient IR was induced in STZ-diabetic rats. DHEA treatment restored H2O2, hydroxyl radical, and reactive oxygen species to close to control levels in normoglycemic rats and significantly reduced the level of all reactive species in STZ-diabetic rats. Moreover, DHEA treatment counteracted the detrimental effect of IR on membrane integrity and function: the increase of lactate dehydrogenase release and the drop in Na/K-ATPase activity were significantly prevented in both normoglycemic and STZ-diabetic rats. The results confirm that DHEA, an adrenal steroid that is synthesized de novo by brain neurons and astrocytes, possesses a multitargeted antioxidant effect. They also show that DHEA treatment is effective in preventing both derangement of the oxidative state and neuronal damage induced by IR in experimental diabetes.

Animals↗

Mutations and immunohistochemistry of p53 and proliferation markers in astrocytic tumors of childhood.

Thirty cases of hemispheric astrocytic tumors of childhood, consisting of 11 pilocytic astrocytomas, 2 fibrillary astrocytomas, 9 anaplastic astrocytomas, and 8 glioblastomas, were studied for the presence of p53 mutations and for immunohistochemical demonstrations of p53 and proliferation markers PCNA and Ki-67 MIB-1. The study was performed using polymerase chain reaction (PCR)-assisted single-strand conformation polymorphism analysis of exons 5-8 and direct sequence analysis of PCR products. For immunohistochemistry, DO1 and PAb 1801 were used. No mutation and no positivity for p53 protein were found in pilocytic astrocytomas. Mutations (at codons 144, 202, and 245) were found in 2 out of 8 glioblastomas and in 1 out of 9 anaplastic astrocytomas, whereas positive staining was found in 11 out of 17 malignant gliomas. Cases with mutations showed the highest p53 labeling index and also PCNA and MIB-1 labeling indices. The negative results in pilocytic astrocytomas are in line with the benign course of these tumors, whereas for malignant gliomas no difference seems to exist in comparison with adult cases.

Adolescent↗

Control of meningioma cell growth by platelet-derived growth factor (PDGF).

We have examined the possible involvement of PDGF and PDGF receptors in the growth control of five meningiomas, analyzing the biopsy specimens and the primary cultures derived from the same tumors. Light and electron microscopy demonstrated that MAbs against PDGF beta-receptors immunodecorate meningioma cells in vivo and in vitro, while those against alpha-receptors gave negative results. The effects of PDGF isoforms AA, AB, BB and of PDGF neutralizing antibodies on meningioma cultures were examined using [3H]thymidine incorporation analysis. Only with PDGF-AB and -BB a mitogenic effect was observed, while PDGF-neutralizing antibodies produced a reduction of [3H]thymidine incorporation. The production of PDGF-like growth factors by meningioma cells was tested analyzing the effects of meningioma culture-conditioned media on the growth of Swiss 3T3 cells. In all cases meningioma conditioned media stimulated the in vitro growth of 3T3 fibroblasts and this stimulatory effect was strongly reduced by PDGF-neutralizing antibodies. Furthermore, Northern blot analysis demonstrated expression of c-sis/PDGF-B and PDGF beta-receptors mRNA in all meningioma biopsies and in all the derived cultures. Our results provide strong evidence that PDGF-B chain and PDGF beta-receptors are involved in growth control mechanisms of human meningiomas through autocrine and/or paracrine mechanisms.

Antibodies, Monoclonal↗