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Biomedical subjects

M Manfredi

Publications and source records attributed to M Manfredi.

At least 109 records · Page 6Linked to original sources

The prevalence of apoE-epsilon4 in Alzheimer's disease is age dependent.

The epsilon4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. However, other yet unidentified factors might be involved. It has been suggested that the epsilon4 allele might be relatively less relevant in Alzheimer's disease with onset before age 60 and after age 80. The aim was to evaluate the association of the epsilon4 allele with Alzheimer's disease across a wide range of ages at onset. 156 patients with age at onset between 46 and 89 and 120 cognitively unimpaired subjects aged 53 to 89 as controls were studied. Age at onset in the cases and age in the controls were stratified into six groups (60 and younger, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and 80 and older). Multivariable sex adjusted probit regression analysis was used to model epsilon4 prevalences in cases and controls across age. The sex adjusted relation of epsilon4 with age in controls was slightly negative with prevalence of 0.16 in the youngest and 0.09 in the oldest age groups. The sex adjusted relation in cases with Alzheimer's disease had a bell shaped curve with prevalence of 0.23 in the youngest age group, rising to 0.54 and 0.51 in the age groups 65 to 69 and 70 to 74, and decreasing to 0.12 in the oldest age group. It is concluded that the relation of the epsilon4 allele with Alzheimer's disease is age dependent, indicating that other risk factors might be relevant in the younger and older ages.

Age Factors↗

Epilepsy provoked by television and video games: safety of 100-Hz screens.

Television (TV) and video games (VG) can provoke seizures in patients with photosensitive epilepsies. Flicker frequency is the most important factor in screen activation. We tested conventional 50-Hz versus 100-Hz monitors during TV viewing and VG playing in 30 photosensitive subjects, 23 of whom had a history of TV or VG seizures or both. Fifteen subjects' discharges were activated by 50-Hz TV; 17 by 50-Hz VG; and one by a 100-Hz screen. Thus, 100-Hz screens protect against screen activation.

Adolescent↗

[International health: a new challenge to nursing education].

A survey was conducted among 110 Schools of Nursing in USA and 5 Schools in Latin America and the Caribbean (LAC) to identify the international health (IH) component in nursing education, practice and research. A significant part of U.S. schools and all 5 LAC schools have international activities, and this interest has started basically in the last 5 to 10 years. There was difference in the structure of IH activities among U.S. and LAC nursing schools, but they were similar in the type of support offered to IH initiatives. IH content in nursing education among U.S. schools was related to culture, health systems and community health; in LAC schools, IH content was related to health promotion, health policy and strategies and nursing perspectives. U.S. and LAC schools with international activities have only 10% of their faculty and students involved with IH initiatives. The nursing schools still lack courses and activities that the Schools of Public Health have implemented to deal with IH. The article observes areas that need to be strengthened so that nursing professionals can expand their leadership roles in research and practice in international health.

Curriculum↗

A model for the explanation of the thermally induced increase of the overall fluorescence in tryptophan-X peptides.

In the range of temperature 10-35 degrees C, Trp-X dipeptides show an unusual increase of fluorescence intensity in solution at pH 7. This effect has been recently studied by means of steady-state fluorescence. Although a model involving the deprotonation at the ground state of the zwitterion was proposed, the activation energy for that process could not rule out the involvement of excited state. In order to understand the mechanism of the thermal-induced increase of fluorescence, we present here time-resolved fluorescence experiments on Trp-X and X-Trp dipeptides at different pH and excitation wave-length. The fluorescence lifetimes (tau i) decrease in accord to thermal quenching, with activation energies (Ei) ranging from 4.0 to 6.4 kcal/mol. Under those circumstances where the anomaly was detected the preexponential factors of the longer-lived component increased as well as their fractional fluorescence. This component can be assigned to the anion species. Because of its larger (three- to fourfold) fluorescence quantum yield, compared to that of the corresponding zwitterion, the large increase of the concentration of the anion leads to an increase of the overall emission despite the thermal quenching. Also the decay-associated spectra well account for the red shift of the emission fluorescence spectrum, which accompanies the anomaly. Our model well fits the experimental data using a simple equation which combines Van't Hoff and Arrhenius equations; it also explains the presence of the anomalous thermal quenching exclusively in Trp-X dipeptides excited above 290 nm and at pH around neutrality.

Calorimetry↗

Corneal reflex responses to mechanical and electrical stimuli in coma and narcotic analgesia in humans.

The corneal reflex, a bilateral eye-blink, can be elicited in humans either by mechanical or electrical corneal stimulation. Both in comatose patients and in normal subjects injected with the opiate fentanyl, the electrically-evoked corneal reflex was more suppressed than the mechanically-evoked reflex. We propose that the mechanical input yields a reflex more resistant to depression of the corticoreticular drive and to narcotic analgesia, because it exploits temporal summation at central synapses, whereas the electrical input exploits spatial summation.

Adult↗

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area.

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons.

Adult↗

Performance of sequential arm movements with and without advance knowledge of motor pathways in Parkinson's disease.

Patients with Parkinson's disease are slower than normal subjects in executing sequential arm movements, and their bradykinesia worsens as the execution of motor sequences progresses. In parkinsonian and normal subjects, we studied the execution of two types of fast sequential arm movements. The subjects had to perform a motor sequence following with their arm a path marked by six targets on a screen. In one experimental condition, they performed the motor sequence without advance knowledge of its path and executed each submovement in response to the consecutive appearance of the targets on the screen (unknown motor sequences). In the other condition, all the targets appeared simultaneously on the screen before the subject moved, and the subject internally determined when to execute each submovement (known motor sequences). Patients were slower than normal subjects in executing both sequences. Patients and normal subjects were faster in executing known than unknown sequences, but the patients' percentage of total movement time diminished less. During the unknown condition, both groups tended to lengthen submovement duration whereas, during the known condition, both groups tended to correct this trend. Patients performed submovements during both sequences with longer acceleration phases. The submovement symmetry ratio of the velocity profile changed according to the direction of movement (up or down). We conclude that these findings depend mainly on the model of movement execution. They also suggest that patients with Parkinson's disease have more difficulty in executing internally determined than externally triggered sequential movements.

Adult↗

Guidelines for the therapeutic use of botulinum toxin in movement disorders. Italian Study Group for Movement Disorders, Italian Society of Neurology.

Since its introduction in the early '80s the use of botulinum toxin has improved the quality of life of the patients affected by movement disorders. Toxin's neuromuscular blocking action allows a symptomatic treatment of those clinical conditions characterised by excessive muscular activity. Although the dosages used are safe and the side-effects are reversible, a correct use of botulinum toxin depends on the knowledge of its clinical pharmacology and of the anatomy of the body segments to be injected. In addition, the treatment of more complex conditions, i.e. laringeal dystonia, imposes an inter-disciplinary approach and specialised injection techniques. In this review, the Italian Study Group on Movement Disorders presents the consensus guidelines for the therapeutic use of botulinum toxin in movement disorders. The main toxin types, their use and administration modalities, and the training guidelines will be presented.

Botulinum Toxins↗

Excitability of the central masticatory pathways in patients with painful temporomandibular disorders.

Much is unclear about the pathophysiological mechanisms underlying painful temporomandibular disorders. In addition to various other theories, masticatory muscle dysfunction and pain have also been attributed to primary central nervous system hyperactivity. We assessed this possibility in a study using recent neurophysiological techniques. From among outpatients whose diagnosis of temporomandibular disorders had been obtained in stomatognathic facilities, we studied 10 patients with bilateral pain and 15 patients with unilateral pain, in whom electromyographic examination of the trigeminal reflexes disclosed normal findings except for absence or amplitude asymmetry of the jaw jerk. Transcranial magnetic stimulation yielded masseter motor evoked potentials of normal latency and amplitude, but five patients had to exert a near-maximum contraction to obtain their responses. The masseter silent periods elicited by the double-shock technique recovered normally. Because these tests measure the excitability of the masticatory system (including motor cortex, corticobulbar and corticoreticular connections, reticular interneurones and lower motoneurones), the lack of facilitation in these patients' responses excluded central hyperactivity as the primary cause of their masticatory dysfunction and pain.

Adult↗

Silent period in upper limb muscles after noxious cutaneous stimulation in man.

We studied the effect of electrical stimulation of the C5-C8 dermatomes on voluntary electromyographic activity (EMG) recorded from the ipsilateral first dorsal interosseus (FDI), abductor digiti minimi, flexor and extensor carpi, triceps brachii, biceps brachii, and orbicularis oculi muscles of healthy humans. Finger stimulation (C6-C8) produced an EMG inhibition (silent period, SP), which progressively decreased in duration from distal to proximal muscles; in the biceps it induced a slight facilitation and in the orbicularis oculi muscle, it had no effect. Stimulation of the C5 dermatome induced no response in either distal or proximal muscles. Only high-intensity stimuli evoked clear silent periods. The threshold for evoking an SP was almost double that required for sensory action potentials, 3.25 times the sensory threshold, and decidedly above the pain threshold. An indirect estimation of the conduction velocity of SP afferent fibres placed them in the A-delta group of myelinated fibres. In double-shock experiments, used to study the recovery cycle of the SP in the FDI muscle after finger stimulation, neither low- nor high-intensity conditioning stimuli delivered 100-500 ms before the test stimulus changed test SPs. Experiments designed to evaluate motoneuronal excitability showed that in relaxed FDI muscle, finger stimulation markedly reduced the F wave at the 50 ms time interval, the time when the SP normally occurs. Our findings demonstrate that the activation of A-delta afferents from the fingers inhibits the C7-T1 motoneurons postsynaptically, through an oligosynaptic spinal circuit. We propose that the strong inhibitory effect exerted by noxious cutaneous stimuli on all distal muscles may contribute to a defence action which is specific for the human upper limb.

Action Potentials↗

Chorea-acanthocytosis: genetic linkage to chromosome 9q21.

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.

Acanthocytes↗

Acetazolamide-responsive episodic ataxia in an Italian family refines gene mapping on chromosome 19p13.

Episodic ataxia type 2 is an autosomal dominant disorder with attacks of vertigo and ataxia which respond to acetazolamide treatment. The gene, distinct from the KCNA1 responsible for episodic ataxia type 1, has been mapped on chromosome 19p13 in a 11-12 cM region. A large Italian kindred affected with acetazolamide-responsive episodic ataxia is reported, with onset in adulthood, a strong vestibular component during attacks and a high frequency of cerebellar vermis degeneration. The genetic analysis (i) showed strong linkage between the disease and the 19p13 microsatellite markers in a region which widely overlaps that previously reported and (ii) set a new distal boundary of the gene-containing region. Combining present and previous mapping data, the gene of episodic etaxia type 2 is most probably located in an interval approximately 1.5 Mb between markers D19S221 and D19S226.

Acetazolamide↗

Eclamptic encephalopathy: imaging and pathogenetic considerations.

Eclampsia is a rare condition peculiar to pregnant and puerperal women, characterized by clinical pre-eclampsia (hypertension, proteinuria, edema) and generalized seizures. Three cases of eclamptic encephalopathy are reported: CT and MRI demonstrated transient abnormalities in the cortical and subcortical regions of the posterior areas of the brain - namely, parieto-occipital lobes - associated with occasional involvement of basal ganglia and/or brainstem. Pathogenesis is still unclear. Strict similarity with the pathological findings characterizing hypertensive encephalopathy suggests that a focal impairment in cerebral autoregulation may be the cause of vasodilation and fluid extravasation leading to hydrostatic edema; selective involvement of posterior areas could be explained by their lesser degree of adrenergic innervation supporting circulatory autoregulation mechanisms.

Adult↗

Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy.

AIMS: To determine whether Parkinson's disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could be useful in the differential diagnosis between the two diseases. METHODS: Sixty two patients (30 with Parkinson's disease and 32 with multiple system atrophy) underwent a complete urodynamic evaluation and neurophysiological testing. RESULTS: Of the parkinsonian patients 36.6% had normal micturition findings with normal bladder sensitivity; 26.7% had delayed or incomplete pelvic floor relaxation; 26.7% had hyperreflexia with vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients with a normal urodynamic pattern had significantly less severe disease and a shorter duration of disease in years than those who had abnormal patterns. Patients with hyperreflexia had significantly higher severity of disease. All the patients with multiple system atrophy had hyperreflexia with synergy. Two urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy correlated neither with the severity nor with the duration of disease. Sphincter EMG analysis showed that all the parkinsonian patients had normal sphincter EMG whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs. CONCLUSIONS: Urodynamic evaluation and sphincter EMG are both useful tests in the differential diagnosis between Parkinson's disease and multiple system atrophy. Urodynamic findings may be abnormal before patients with multiple system atrophy reach an advanced stage of the disease. Recordings of EMGs from perineal muscles become abnormal as the disease progresses in multiple system atrophy but not in Parkinson's disease.

Aged↗

Taxol pretreatment of tumor targets amplifies natural killer cell mediated lysis.

Taxol is known to polymerize and stabilize microtubules and thereby alter many cellular functions. Our studies examined the effects of taxol pretreatment of tumor targets and cytotoxic effector cells in an effort to determine whether such treatment would result in increased tumor cell lysis without affecting cytotoxic cell function. Our studies demonstrated that taxol concentrations of 6-30 ng/ml which induced approximately 50% growth inhibition and > or = 50% block in the G2/M phase of the K562 cell targets did not have any significant effect on the functional ability of NK cells to lyse K562 cells. Pretreatment of K562 cells with taxol (6 and 30 ng/ml) resulted in an increase in K562 cell lysis by NK cells (or NK cells stimulated with 100 units/ml of rIL-2) in 7 out of 9 donors. The amplification of NK cell-mediated lysis of tumor targets due to taxol pretreatment may provide a combination therapeutic approach which includes taxol treatment followed by rIL-2 stimulation of the immune killer cell function.

Antineoplastic Agents, Phytogenic↗