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Biomedical subjects

F Benvenuti

Publications and source records attributed to F Benvenuti.

At least 19 recordsLinked to original sources

Optimised procedure for the calibration of the force platform location.

An innovative optimised method, including an experiment and a mathematical model, for the calibration of the force platform location in the optoelectronic reference frame is proposed. The calibration experiment adopts a bearing-marker testing object contacting the platform and does not directly measure the platform location. The experiment is designed in order to avoid the main drawbacks possibly occurring in commonly adopted methods. The mathematical model of the experiment estimates the expected ground reaction. An optimisation algorithm identifies the optimal platform location as the one that best matches the measured outcome of the calibration experiment with the corresponding model estimate. The innovative calibration procedure has been assessed in terms of inter-tester reliability and compared with commonly used calibration procedures of platform location. These results evidenced how the introduction of such optimised procedure could improve the reliability of the calibrated platform location and, consequently, of the kinetic variables considered in posture and gait analysis.

Algorithms↗

Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study.

OBJECTIVES: Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. METHODS: We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. RESULTS: In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. CONCLUSIONS: In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.

Adult↗

Genetic vaccination for the immunotherapy of B-cell malignancies.

Vaccination protocols based on targeting of the idiotype expressed on malignant B cells have so far provided encouraging results in clinical trials. The essential requirement to induce an immune response is the inclusion of carriers to overcome T-cell tolerance. Chemical cross-linking of idiotypic protein is so far the method of choice to induce protective responses in human studies. Meanwhile, a flurry of alternative strategies to simplify vaccine production is being tested in murine model. Thanks to the advance in antibody engineering the two relevant antigenic domains of the lymphoma immunoglobulin can be assembled into an appropriate format, genetically linked to molecules that act as immunological adjuvants and directly delivered as plasmid DNA. Upon immunization, rejection of tumor cells may depend on cellular or humoral mechanisms, whose relative importance has not been entirely estimated. We have recently analyzed the specificity of anti-idiotypic antibodies induced by DNA vaccination and characterised the elements contributing to optimal anti-idiotypic responses.

Animals↗

Effects of low frequency electromagnetic fields on expression of lymphocyte subsets and production of cytokines of men and women employed in a museum.

The objective of this study was to analyse the immune response to electromagnetic fields (ELMFs) in seven men and eight women employed in a museum. The workers were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39 men with a similar percentage of atopic subjects, age (range 30-51 years) and smoking habits of the workers included in the study. Levels of blood lead (Pb) and urinary trans-trans muconic acid, a metabolite of benzene (markers of exposure to traffic and smoking) of the control and exposed groups were similar. Lymphocyte subsets were determined in men and women using conjugated antibodies. Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA), as well as blastogenesis of PMBCs induced by PHA, were determined in women only. ELMF-exposed women showed a significant reduction in the percentage of B and NK CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes. They also showed significantly lower levels of interferon gamma in serum, or produced in the supernatants by PMBCs both spontaneously and stimulated by PHA, while they did not show significant changes in serum and 'in vitro' produced IL-4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to the controls, a statistically significant reduction in both number and percentage of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this investigation demonstrates a reduction of blood NK lymphocytes and of the production of interferon gamma in workers exposed to low frequency ELMFs. Recent studies have shown that stress and poor lifestyle induce the reduction of blood cytotoxic activities possibly acting on nervous functions. This may suggest that ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous systems.

Adult↗

Spot check of the calibrated force platform location.

In a movement analysis laboratory, stereophotogrammetric motion capture systems and force platforms must share one absolute reference frame that allows the computation of joint moments and powers. The correct calibration of the platform location identifies the transformation between force plate and absolute reference systems, which determines the spatial coherence among the equipments' measurements. The aim of this study was to develop and test a spot check for the assessment of platform location calibration. Platform location calibration was assessed by comparing the measured outcome of an experiment performed with a pointed rigid rod bearing a set of markers with the corresponding expected results, computed with a model. A set of indices was then proposed to define a confidence volume in which the true ground reaction force is expected to be. The spot check was applied to a real laboratory setup and the effects of simulated platform mislocations were analysed. It was verified that the hip joint moment may be equally affected by a single marker misplacement of about 20mm during platform location calibration, an occurrence that was clearly identified by the spot check, and by a hip centre location inaccuracy of 30mm.

Biomechanical Phenomena↗

Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined V(L)/V(H) determinants.

DNA vaccines encoding the idiotype of immunoglobulins of tumour B cells were shown to induce protection in several mouse lymphoma models. The mechanism of rejection of tumour cells has not been fully understood, but there is strong evidence suggesting that engagement of the idiotype by anti-idiotypic antibodies may directly result in inhibition of tumour growth. In this study, we have investigated the structural basis of the idiotypic/anti-idiotypic interaction following immunisation with DNA vaccines. scFvs containing only one of the two tumour-derived V regions recombined to an irrelevant V region partner were generated. These constructs encoding a secretory form of the scFv were used as immunogens to induce anti-Id antibodies. The same scFvs were expressed as membrane-bound molecules on the surface of mammalian cells. Analysis of immune sera on the membrane-displayed idiotypes revealed that DNA immunisation induced a polyclonal antibody response restricted to conformational combined epitopes formed by the parental V(L)/V(H) association. Immune sera raised by scFv DNA vaccination did not show any detectable reactivity towards chimeric scFvs containing only one of the two immunising V regions, indicating that the response against combined V(L)/V(H)determinants is highly dominant. Remarkably, the same immunogen, delivered as scFv protein, induced antibodies also directed against chain-specific determinants. These findings indicate that presentation of properly folded idiotypes results in a highly specific antibody response directed exclusively to private idiotypic determinants of the V(L)/V(H) combination of the immunogen.

Animals↗

Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Adult↗

Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for tumor protection.

Vaccination with immunogenic formulations of lymphoma-derived immunoglobulin can elicit strong anti-idiotypic immune responses which have proved effective in murine B cell tumor challenge experiments and suggested possible benefits in recent human clinical trials. Naked plasmid DNA vaccines encoding the Id determinants as scFv fragments provide the most promising alternative to protein immunization. With this approach the addition of an immunogenic domain linked to the scFv has proved essential for the induction of a protective immune response. In this study we have produced a scFv gene construct linked to the CH3 exon of the human IgG1 constant region and tested its efficacy in inducing protective immunity against the mouse BCL1 lymphoma. We have also generated a second construct in which the BCL1 VL gene was deleted to investigate whether the VH region domain contains sufficient antigenic determinants for a protective immune response. Both constructs induced anti-idiotypic antibodies that specifically reacted with the BCL1 IgM protein in ELISA and with BCL1 tumor cells in flow cytometry assays. Protection against tumor challenge was fully achieved with the complete scFv construct whereas immunization with the construct lacking the VL gene resulted in only a slight prolongation of the survival. We therefore conclude that a plasmid DNA vaccine containing the VH and VL genes of the lymphoma Ig linked to the human IgG1 CH3 exon is highly effective in inducing a protective immune response in the BCL1 model. We also demonstrated that VH gene immunization can induce strong anti-idiotypic antibody responses.

Animals↗

Measuring muscular strength of the lower limbs by hand-held dynamometer: a standard protocol.

The aim of this study is to describe the reliability of measuring maximal strength of eight muscle groups of the lower limb by a hand-held dynamometer, according to a standard assessment protocol. The study population consisted of 26 patients (14 males and 12 females; age range 60-90 years) admitted to a geriatric hospital. Multiple assessments of muscle strength by two different examiners were compared to estimate test-retest and inter-rater reliability. The range of strength evaluated across the eight muscle groups was 2.1-29.8 Kg/force. Overall, short-term (same day) and long-term (one week apart) test-retest and inter-rater reliability were very high, with 60% of the intraclass correlation coefficient values above 0.8, and the majority above 0.7. No significant differences in strength were found comparing the left and the right side of each muscle group. Differences between values collected in the same subject by two different examiners, and by the same examiner at different points in time were similar, not influenced by the average strength of the muscle group, and significantly larger for long-term than for short-term comparisons. By using a standardized measurement protocol, reliable measurements of muscle strength can be obtained by a hand-held dynamometer in frail older persons.

Aged↗

Are perception and action affected differently by the Titchener circles illusion?

In the present study, we investigated the effects of the Titchener circles illusion in perception and action. In this illusion, two identical discs can be perceived as being different in size when one is surrounded by an annulus of smaller circles and the other is surrounded by an annulus of larger circles. This classic size-contrast illusion, known as Ebbinghaus or Titchener Circles Illusion, has a strong perceptual effect. By contrast, it has recently been demonstrated that when subjects are required to pick up one of the discs, their grip aperture during reaching is largely appropriate to the size of the target. This result has been considered as evidence of a clear dissociation between visual perception and visuomotor behaviour in the intact human brain. In this study, we suggest and investigate an alternative explanation for these results. We argue that, in a previous study, while perception was subjected to the simultaneous influence of the large and small circles displays, in the grasping task only the annulus of circles surrounding the target object was influential. We tested this hypothesis by requiring 18 subjects to perceptually estimate and grasp a disc centred in a single annulus of Titchener circles. The results showed that both the perceptual estimation and the hand shaping while grasping the disc were similarly influenced by the illusion. Moreover, the stronger the perceptual illusion, the greater the effect on the grip scaling. We discuss the results as evidence of an interaction between the functional pathways for perception and action in the intact human brain.

Adult↗

Expression of lymphocyte subpopulations, cytokine serum levels, and blood and urinary trace elements in asymptomatic atopic men exposed to an urban environment.

The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.

Case-Control Studies↗

Kinematic characteristics of standing disequilibrium: reliability and validity of a posturographic protocol.

OBJECTIVE: To investigate retest reliability and concurrent validity of the fundamental measurements made of a posturographic protocol that employs quiet standing to quantify the severity and the nature of patients' postural disturbances. STUDY DESIGN: Retrospective complete block design. SETTING: Geriatric rehabilitation department. PARTICIPANTS: Thirty-six participants (age range, 67 to 86 yrs) having normal, moderate, or severe levels of disequilibrium. METHODS: Quiet standing was evaluated on three occasions using a three-dimensional motion analysis system and a force platform. Eight testing conditions, designed to vary task difficulty by controlling the contributions of vision, foot proprioception, and base-of-support width, were administered. MAIN OUTCOME MEASURES: Retest reliability of body sway, joint alignment, body position, and motor coordination indicators were evaluated by intraclass correlation coefficients (ICCs). Concurrent validity of protocol measures was evaluated by the prediction of disequilibrium from a stepwise linear discriminant analysis. RESULTS: ICCs indicated high level of retest reliability for all variables but those of motor coordination, which was not influenced by testing conditions. Discriminant analysis resulted in a four-factor discriminator that included measures of body sway, position, alignment, and motor coordination. The derived linear discriminate function correctly classified 96% of the patients' level of disequilibrium. CONCLUSIONS: The posturographic protocol has the potential to be a useful tool for evaluating severity and nature of postural instability and the effects of pharmacologic and rehabilitative treatment. Results also indicate that combining direct body measurements with force-plate data has the potential to expose the underlying impairments that cause disequilibrium, determine their pathogenesis, and evaluate compensatory strategies.

Aged↗

Is the telephone interview for cognitive status a valid alternative in persons who cannot be evaluated by the Mini Mental State Examination?

The Mini Mental State Examination (MMSE), a widely used tool for first-line assessment of cognitive function, cannot be fully administered to persons with severe visual or upper extremity impairments. This cross-sectional study, which was performed in a sample of patients admitted to the outpatient clinic of the INRCA Geriatric Department "I Fraticini" (Firenze, Italy) and their relatives, evaluated whether the Telephone Interview for Cognitive Status (TICS), a test originally created for telephone screening of cognitive impairment, is a valid alternative for assessment of cognition in persons who cannot provide valid responses to all the MMSE items. Fifteen subjects in each of seven MMSE strata (9-11, 12-14, 15-17, 18-20, 21-23, 24-26, 27-30) were consecutively selected. Inclusion criteria were: age > or = 60 years; Italian as the main language; education > or = 3 years; medical stability; and ability to complete the MMSE. At admission, participants were examined for dementia by an expert clinician according to the DSM IV criteria. Italian versions of the TICS and the MMSE were administered face-to-face by two trained interviewers. The TICS was readministered face-to-face one week later by the same interviewer that had previously administered the test. The TICS showed good test-retest reproducibility. Assessments taken one week apart differed on average by 0.52 +/- 1.9 points (p < 0.01), indicating a systematic improvement. The TICS explained 96% of the variance in the MMSE, and this association was independent of age, gender and education. More than 90% of the cases "screening positive" (i.e., scoring below a certain cut-off) by the TICS, were also identified as "screening positive" when comparable MMSE cut-off scores were used. Using comparable cut-off scores, the sensitivity and specificity of TICS and MMSE in detecting a standard clinical diagnosis of dementia largely overlapped. In persons who cannot be evaluated with the MMSE in its full form, the face-to-face administration of the TICS is a reliable and valid alternative.

Aged↗

Defective motor control of coughing in Parkinson's disease.

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.

Abdominal Muscles↗