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Biomedical subjects

P Pasqualetti

Publications and source records attributed to P Pasqualetti.

At least 91 records · Page 5Linked to original sources

Modulation of corticospinal output to human hand muscles following deprivation of sensory feedback.

Excitability and conductivity of corticospinal tracts of 10 volunteers were investigated by motor-evoked potentials (MEPs) to transcranial magnetic brain stimulation, before and after anesthetic block of right median (sensory + motor) and radial (sensory) nervous fibers at the wrist. MEPs were simultaneously recorded from two ulnar-supplied muscles during full relaxation and voluntary contraction. These muscles maintained an intact strength following anesthesia, but they were in a remarkably different condition with respect to the surrounding skin: the first dorsal interosseous muscle (FDI) was totally "enveloped" within the anesthetized area but was still dispatching a normal proprioceptive feedback; the abductor digiti minimi (ADM) was preserving both cutaneous and proprioceptive information. Spinal and peripheral nerve excitability were monitored as well. The sensory deprivation induced short-term changes which selectively took place within the hemisphere connected to the anesthetized hand. The physiological latency "anticipation" of MEPs recorded during active contraction versus relaxation was reduced (P < 0.001) in the FDI, but not in the ADM, when values during anesthesia were compared with preanesthesia values. The FDI cortical representation-as analyzed by a mapping procedure of the motor cortex via focal stimuli of several scalp positions-was significantly (P < 0.002) reduced, while the ADM representation remained either unchanged or enlarged. MEP and F-wave variability significantly decreased in the FDI but not in the ADM. F-waves were also affected due to changes in the motoneuronal excitability at spinal level. Peripheral nerve and root stimulation showed no modifications. Results are discussed in view of the short-term modifications of the corticospinal pathway somatotopy produced by the selective reduction of the sensory flow. Implications of the sensory feedback in motor control are also discussed.

Contingent Negative Variation↗

A neuromagnetic normative data set for hemispheric sensory hand cortical representations and their interhemispheric differences.

Somatotopy of human hand primary sensory cortex has been studied neuromagnetically [C. Baumgartner, A. Doppelbauer, L. Deecke, D.S. Barth, J. Zeitlhofer, G. Lindinger, W.W. Sutherling, Neuromagnetic investigation of somatotopy of human hand somatosensory cortex, Exp. Brain Res. 87 (1991) 641-648.] [1]. Investigation of sensory cortex devoted to the hand will be of major importance in relation to clinical recovery after sensorimotor deficits as well as an index of plasticity phenomena following alterations of peripheral nerves inputs. Here a normative data set has been constructed, on the basis of the neuromagnetic investigation of the primary sensory hand cortical representation in the two hemispheres of 20 healthy volunteers. This can be used to evaluate interhemispheric differences of the 'sensory' hand areas during experimental paradigms in the healthy as well as following patients with monohemispheric lesions. The localizations in each hemisphere of the cortical Equivalent Current Dipoles (ECDs) activated with the shortest latencies (N20m and P30m components) by separate stimulation of left and right median nerve, thumb and little finger were analysed. By considering the ECDs to thumb and little finger stimulation the boundaries of the hand cortical representation in primary sensory cortex, the 'hand extension' was measured as the distance between the two. For all the considered parameters (related to N20m and P30m ECDs: latency, strength, spatial position in the individual head, 'hand extension', interhemispheric differences) the appropriate variable distribution was considered and by including the 98% of the healthy population normative limits were calculated.

Adult↗

Circadian rhythm of arginine vasopressin in hepatorenal syndrome.

The etiology of hepatorenal syndrome is still incompletely understood, but the nonosmotic release of arginine vasopressin (AVP) seems to have an important role. Since AVP presents a well-defined daily periodicity in its production and secretion, the aim of the study was to investigate the circadian rhythm in its circulating plasma concentrations in patients with hepatorenal syndrome, compared with healthy controls. Venous blood samples were drawn during a 24 hour period at 2 hourly intervals from a peripheral vein in 10 healthy subjects and in 10 patients with hepatorenal syndrome for the determination of the circulating plasma levels of AVP by radioimmunoassay. Statistical analysis was carried out by the 'cosinor' method. The controls presented a significant (p < 0.002) circadian rhythm in the AVP circulating levels, whereas no rhythm (p > 0.05) was found in patients. The circadian rhythms were significantly (p < 0.005) different between the two groups, patients having higher mean daily concentration and lower circadian variation of AVP. These results confirm the existence of a well-defined circadian rhythm of AVP in healthy subjects, whereas the hepatorenal syndrome patients present a complete loss of the circadian rhythm. It could be hypothesized that primitive damage in circadian time-keeping regulates the circadian rhythm of vasopressinergic neurons, or has a secondary effect on the peripheral vasodilatation in the course of advanced liver disease. This great upset in the temporal and functional organization, together with that of the renin-angiotensin-aldosterone system, could play an important role in promoting and/or in the maintenance of the hydroelectrolyte imbalance that characterizes the hepatorenal syndrome.

Arginine Vasopressin↗

Plasma levels of arginine vasopressin in hepatorenal syndrome.

BACKGROUND: The etiology of hepatorenal syndrome is still incompletely understood, but the non-osmotic release of arginine vasopressin (AVP) seems to have an important role in its pathogenesis. The aim of the study was to investigate the circulating plasma concentrations of AVP in patients with hepatorenal syndrome, compared with healthy controls, in relation with plasma osmolality. METHODS: Venous blood samples were drawn in 20 healthy subjects and in 20 patients with HRS for the determination of the plasma levels of AVP by radio-immunoassay and of plasma osmolality. The comparison between the two groups was carried out by the Student "t"-test for unpaired data; the plasma AVP levels were correlated with the values of plasma osmolality by linear regression analysis. RESULTS: The patients presented significantly (p < 0.001) higher plasma AVP levels in respect to controls; on the contrary, plasma osmolality was significantly lower in patients than in controls (p < 0.005). Whereas a significant (r = 0.83; p < 0.001) relationship was demonstrated between plasma AVP and osmolality in controls, no significant (r = 0.23; p > 0.05) correlation was found in patients. CONCLUSIONS: These results confirm the existence of an activation in the release of AVP in hepatorenal syndrome, due to the activation of the sympathetic adrenal system and to hyponatriemia. The contraction of diuresis in hepatorenal syndrome, on the other hand, is not due to a deficiency in plasma AVP. AVP release occurs despite low plasma osmolality, which normally inhibits its secretion. This great upset in functional organization, together with that of the atriopeptin-renin-angiotensin-aldosterone system, could play an important role in promoting and/or in the maintenance of the hydro-electrolyte imbalance that characterizes the syndrome.

Aged↗

Circadian rhythms of plasma atriopeptin, plasma renin activity and plasma aldosterone in patients with hepatorenal syndrome.

The etiology of hepatorenal syndrome (HRS) is still incompletely understood, but the atriopeptin-renin-aldosterone system plays an important role in its pathogenesis. Since this system presents a circadian rhythmicity, the aim of the study was to investigate the circadian rhythm in the circulating concentrations of atriopeptin (atrial natriuretic peptide, pANP), plasma renin activity (PRA) and plasma aldosterone (pA) in patients with HRS, compared with healthy controls. Venous blood samples were drawn during the span of a whole day and every two hours from a peripheral vein in 10 healthy subjects and in 10 patients with HRS. The circulating concentrations of pANP, PRA and pA were determined by radioimmunoassay. Statistical analysis was carried out by the "cosinor" method. The controls presented a significant (p < 0.05) circadian rhythm for each variable, whereas no rhythm (p > 0.05) was found in HRS patients. The pANP, PRA and pA rhythms were significantly (p < 0.05) different between the two groups, HRS patients having higher mean daily concentrations and larger circadian variations of pANP, PRA and pA than controls. Significant relations (p < 0.05) were demonstrated between the mean daily concentrations of pANP and PRA (r = 0.79), PRA and pA (r = 0.73) and PRA and pA (r = 0.76) in the controls; on the contrary, the HRS patients showed only a significant (p < 0.05) positive relation between pANP and PRA (r = 0.71). These results confirm the previous observation that the atriopeptin-renin- aldosterone system presents a well-defined circadian time structure in healthy subjects, while the HRS patients present a complete loss of the secretory sequentiality and of the circadian rhythm, with desynchronization of the whole system. This great upset in the temporal and functional organizations of the system could play an important role in promoting and/or in maintaining the hydro-electrolyte unbalance of HRS.

Aldosterone↗

Monoclonal gammopathy of undetermined significance evolving directly in primary plasma cell leukemia.

A case of monoclonal gammopathy of undetermined significance (MGUS) which evolved directly into primary plasma cell leukemia (PCL) is reported. Even if MGUS and PCL represent the opposite aspects of the same immunoproliferative disorder, no previous cases of this direct evolution have been described, as stated by an accurate review of the specific literature. The patient abruptly developed PCL after five months from the discovery of a serum monoclonal spike, without any other clinical, laboratory and radiological abnormalities. The practical conclusions of this case report indicate that a patient with MGUS must be followed periodically and over an indefinite period, and that PCL must be considered into the possible evolution of MGUS.

Humans↗

Risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance.

The acturial probability of malignant transformation was analyzed in a series of 263 patients with monoclonal gammopathy of undetermined significance (MGUS) over a 15-year period and followed from 5 to 20 years. At a median follow-up of 11.5 years, 157 patients (59.7%) had died of causes unrelated to MGUS, 47 (17.9%) were still alive and presented no increase in monoclonal component, 11 (4.1%) presented an increase in monoclonal component without evidence of malignant immunoproliferative disease, and 48 (18.3%) had developed a malignant transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia, three of malignant lymphoma, two of amyloidosis, one of chronic lymphocytic leukemia, and one of plasma cell leukemia. The cumulative incidence of malignant transformation was 18.3%; and the actuarial risk of malignant transformation was 6.1, 15.4, and 31.3% at 5, 10 and 20 years, respectively. The multivariate regression analysis according to Cox's proportional hazard model selected among 22 different variables established at initial diagnosis of MGUS only age as the factor significantly (P < 0.011) and negatively (b = -1.104) related to the risk of developing a malignant immunoproliferative disease. Therefore, patients with MGUS present an increased risk of developing a malignant lymphoproliferative or plasma cell proliferative disease, and MGUS could be considered a pre-neoplastic condition. Since no clinical or laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up periodically and over an indefinite period.

Actuarial Analysis↗

Tobacco smoking and risk of haematological malignancies in adults: a case-control study.

A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute nonlymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose-response effect, and the variation in risk according to the histological subtype of the malignancy.

Adolescent↗

Cosinor analysis of circadian peak expiratory flow variability in normal subjects, passive smokers, heavy smokers, patients with chronic obstructive pulmonary disease and patients with interstitial lung disease.

Peak expiratory flow (PEF) presents a circadian rhythm with a maximum in the afternoon, and a significant variability in its diurnal variations has been reported in normal subjects and in chronic obstructive pulmonary disease (COPD). In order to investigate whether passive smoking, active tobacco smoking, COPD and interstitial lung disease (ILD) are associated with changes in the circadian rhythm of PEF, five groups of adult male subjects, comparable for age, weight and height, were studied: group A: 30 clinically healthy subjects who never smoked, group B: 30 subjects passively exposed to tobacco smoking, group C 30 heavy smokers (> 20 cigarettes daily for at least 5 years), group D: 30 patients with nonasthmatic COPD (emphysema and/or chronic bronchitis), and group E: 15 patients with ILD (pneumoconiosis). Active tobacco smoking and exposure to passive smoking were assessed by the determination of the urinary cotinine concentration. A portable spirometer was used to measure PEF over a whole day, at 0.00, 6.00, 8.00, 10.00, 12.00, 14.00, 16.00, 18.00, 20.00, 22.00, and 24.00 h, all subjects leading a normal life. The 'mean cosinor' method was used for statistical analyses; the PEF variability was evaluated by the amplitude percent mesor (daily mean). All groups showed diurnal fluctuations in PEF values with significant (p < 0.05) circadian rhythms. The peaks of PEF rhythms occurred in the early afternoon, without significant (p > 0.05) differences between the groups. The cosinor mean was significantly (p < 0.05) lower in heavy smokers, in passive smokers, and in COPD patients than in controls. Controls, passive smokers, heavy smokers, COPD and ILD patients presented a PEF amplitude percent mesor (95% confidence limits) of 6.26% (range 4.57-7.95), 7.79% (range 5.07-10.51), 12.60% (range 7.61-17.59), 17.19% (range 10.18-23.50), and 3.98% (range 2.09-5.87), respectively, with significant differences (p < 0.05) between all groups, except between controls and passive smokers. These data suggest that tobacco smoke, both passive and active, does not modify the circadian peak of PEF, but modifies significantly its mesor and amplitude. In this respect, heavy smokers have the same pattern of COPD: lower mesor and greater amplitude; passive smokers present an intermediate situation. An increased diurnal variability in PEF could be considered as an early index of tobacco smoke damage and of developing COPD. When studying diurnal PEF variability, active and passive smoking habits should be considered.

Adult↗

The natural history of monoclonal gammopathy of undetermined significance. A 5- to 20-year follow-up of 263 cases.

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum monoclonal component (M-component), but no evidence of multiple myeloma, macroglobulinaemia, amyloidosis or other plasma cell proliferative disease. A long-term follow-up study (median 11.5 years) has been carried out in 263 cases of MGUS, 159 males (60.5%) and 104 females (39.5%), aged 40-89 years (median 66.5 years). The actuarial probability for malignant transformation was 6.1, 15.4 and 31.3% at 5, 10 and 20 years, respectively. At the final evaluation, 157 patients (59.7%), 119 (45.3%) of whom with no increase and 38 (14.4%) with an increase in serum M-component, died of causes unrelated to MGUS and without development of any plasma cell proliferative disease; 47 patients (17.9%) were still alive without increase in M-component; 11 patients (4.1%) were still alive and at follow-up presented values of serum M-component > 30 g/l without any evidence of plasma cell proliferative or lymphoproliferative disease; 48 patients (18.3%) developed multiple myeloma (35 cases, 13.1%), solitary plasmacytoma of the bone (2 cases, 0.8%), macroglobulinaemia (4 cases, 1.6%), malignant lymphoma (3 cases, 1.2%), amyloidosis (2 cases, 0.8%), chronic lymphocytic leukaemia (1 case, 0.4%), and plasma cell leukaemia (1 case, 0.4%). The patients developing multiple myeloma, solitary plasmacytoma, macroglobulinaemia and plasma cell leukaemia had an increase in serum M-component, whereas no increase was found in malignant lymphoma, amyloidosis and chronic lymphocytic leukaemia. These findings and the data in the literature suggest that MGUS could be considered a preneoplastic condition; since no clinical and laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up indefinitely.

Adult↗

No influence of aging on the circadian rhythm of erythropoietin in healthy subjects.

The diurnal rhythm in the circulating serum levels of erythropoietin (Epo) was investigated in a group of 20 clinically healthy subjects aged 30-55 years and in a group of 20 healthy subjects aged 55-75 years. Venous blood samples were drawn during the span of a whole day every 4 h, starting from midnight, for the determination of serum Epo levels by radioimmunoassay. Statistical analysis was carried out by means of the 'cosinor' method. Both groups presented a significant (p < 0.05) circadian rhythm in serum Epo levels, with maximum in the afternoon. The younger subjects had significantly (p < 0.05) higher mean daily levels and higher diurnal variations of serum Epo than older subjects; no difference (p > 0.05) was found between the groups regarding the peaks of the rhythms. These data confirm the presence of a circadian rhythm in serum EPO levels and suggest that the aging process does not influence the physiological diurnal fluctuations but modifies the mean daily levels and the amplitude of the diurnal variations, such as it occurs for many other variables. This behavior is an index of aging, but does not seem to have clinical implications.

Adult↗

Contribution of central neuropathy to postural instability in IDDM patients with peripheral neuropathy.

OBJECTIVE: To evaluate the contribution of central neuropathy on postural impairment observed in diabetic patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS: Central sensory and motor nervous propagation, nerve conduction velocity, and static posturography were assessed in the following age-matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM patients without peripheral neuropathy (group D), and 31 control subjects (group C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were recorded, and the spine-to-scalp sensory central conduction time (SCCT) was evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during magnetic transcranial brain stimulation, and the scalp-to-spine motor central conduction time (MCCT) was evaluated. The following posturographic parameters were calculated from the statokinesigram: trace length, trace surface, velocity of body sway with its standard deviation, and VFY (a parameter derived from the velocity variance and the anteroposterior mean position of the body). RESULTS: SCCT was significantly higher in the DN group than in the C and D groups (P < 0.001). MCCT was similar in all groups. Posturographic parameters were all significantly impaired in the DN group (P < 0.01). While posturographic parameters showed a direct relationship with some parameters of peripheral nerve conduction, no correlations were observed with SEP and MEP central conduction time. These results were also confirmed by logistic regression, which indicates peripheral neuropathy as the only implicating factor in postural instability (odds ratio 0.22, 95% CI 0.07-0.75) after data reduction by means of factor analysis. CONCLUSIONS: Although diabetic patients with peripheral neuropathy show a delay in central sensory conduction, postural instability may be fully explained by the presence of peripheral neuropathy.

Adult↗

Diurnal rhythm of serum erythropoietin circulating levels in chronic obstructive pulmonary disease.

OBJECTIVE: Since erythropoietin (Epo) presents a diurnal rhythm in its circulating serum levels and it is reported increased in patients with chronic obstructive pulmonary disease (COPD), the circadian rhythm of Epo was investigated in a group of 40 normocytemic patients with chronic obstructive pulmonary disease compared with 40 clinically healthy subjects. METHODS: Venous blood samples were drawn in each subject during the span of a whole day every four hours, starting from midnight, for the determination of serum Epo levels by RIA. Statistical analysis was carried out by chronograms and by means of the "cosinor" method. RESULTS: The control group presents a significant (p < 0.001) circadian rhythm in serum Epo levels, with maximum in the afternoon, whereas no rhythm (p > 0.05) is detected in the patient group. This has significantly (p < 0.05) higher mean daily levels and lower diurnal variations of serum Epo than the control group; a significant (p < 0.05) difference exists between the two groups regarding the peaks of rhythms. CONCLUSION: These data confirm the presence of circadian rhythm in serum Epo levels and suggest that the COPD, by daytime hypoxemia with associated severe nocturnal desaturation, is associated with increased serum Epo levels both by day and by night, so that the physiological circadian rhythm is lost in these patients.

Adult↗

Focal brain stimulation in healthy humans: motor maps changes following partial hand sensory deprivation.

Cortical motor maps of first dorsal interosseus (FDI), abductor digit minimi (ADM) and wrist flexors muscles were produced following transcranial focal magnetic stimulation of the contralateral motor areas in seven volunteers. Motor evoked potentials (MEPs) were recorded before and during median and radial nerves anaesthetic block at wrist. Results indicated that the FDI muscle cortical representation was significantly reduced; this muscle was entirely "enveloped' in the hand region deprived of its cutaneous sensory information, despite maintaining its usual proprioceptive feed-back and strength via the ulnar nerve. On the contrary, the ADM (serving as "control condition' because outside the anaesthetised hand area) cortical representation was unchanged, even if showing a tendency to enlarge in the topographic maps. No amplitude changes of compound muscle action potentials of ADM and FDI during peripheral stimulations were observed, while changes in F-wave responses were detected in both muscles. No significant topographic changes were found for the wrist flexors muscles. A possible explanation for these "short term' rearrangements of brain motor maps is given on the basis of neural plasticity mechanisms due to the loss of tonic cutaneous inputs on cortical and spinal motoneurons.

Anesthesia, General↗

Risk of monoclonal gammopathy of undetermined significance: a case-referent study.

A retrospective study was conducted in 285 cases of monoclonal gammopathy of undetermined significance (MGUS) and in 570 sex- and age-matched hospital controls in order to investigate the possible association between socioeconomic status, residence, alcohol and tobacco habits, occupation, occupational exposure to toxic substances, chronic antigenic stimulation, and risk of MGUS. Significant associations with the risk of MGUS were found for farmers (P < 0.005) and for workers in industry (P < 0.025). Occupational exposure to asbestos, fertilizers, mineral oils and petroleum, paints and related products, pesticides, and radiation was significantly (P < 0.05) associated with an increase in risk of MGUS. Chronic immune-stimulating conditions, when considered as a group, presented a significant (P < 0.025) association with the risk of MGUS, but no specific disease has been found to be significantly associated. These data are in agreement with the previous reports on multiple myeloma, suggesting that these factors may play an important role in the development of monoclonal gammopathies. However, these findings need to be confirmed in prospective larger population-based studies.

Adult↗

Circadian rhythm of serum erythropoietin in multiple myeloma.

The diurnal rhythm in the circulating serum levels of erythropoietin (EPO) were determined in a group of 20 adult clinically-healthy subjects, in a group of 10 patients with myeloma without renal impairment and 10 patients with myeloma and renal failure. Venous blood samples were drawn during the span of a whole day and every 4 hr, starting from midnight, for the measurement of serum EPO levels by radioimmunoassay (RIA). Statistical analysis was carried out by means of the "cosinor" method. Results show that the controls and the myeloma patients without renal insufficiency present significant (P < 0.05) circadian rhythms in serum EPO levels; no rhythm (P < 0.05) was detected in patients with myeloma and renal failure. Patients with myeloma and renal failure have significant (P < 0.05) lower mean daily levels and diurnal fluctuations of EPO than the other groups, whereas the patients with myeloma without renal involvement present higher (P < 0.05) mean daily levels and lower (P < 0.05) diurnal variations of EPO than controls; no differences (P > 0.05) exist between the groups regarding peaks of rhythms. These data confirm the existence of a physiological circadian rhythm in serum EPO concentrations, with maximum in the afternoon, and they suggest that renal failure is an important cause of anemia and loss of EPO circadian rhythm in patients with myeloma.

Aged↗