Biomarkers of aging and survival kinetics.
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Biomedical subjects
Publications and source records attributed to A Basso.
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Phonological short-term memory was investigated in 24 aphasic left brain-damaged patients and in 12 matched controls. Aphasic patients have a reduced auditory and visual immediate memory span and show the standard detrimental effect of phonological similarity on immediate retention only when the stimuli are auditorily presented, while in the control group the effect is present with both auditory and visual input. Most patients have phonological processing deficits, but two patients have an impaired immediate verbal memory in the absence of analysis disorders. These results, in line with most individual case studies of patients with selective deficits of verbal short-term memory, are interpreted with reference to a model distinguishing a phonological short-term store component of memory, to which auditory input has direct and automatic access, and a rehearsal component, that, after phonological recoding, conveys visually presented stimuli to the phonological store. This latter system, that appears to become fully operational later in development, is less resistive to brain damage.
Oxidative stress may affect cardiac function and metabolism. Oxidants are normally inactivated by reacting with reduced glutathione (GSH), with resulting formation and release of oxidized glutathione (GSSG). However, ischemia might affect glutathione metabolism. This might render ischemic hearts less resistant against subsequent oxidant injury during reperfusion, and it might also affect the reliability of GSSG measurements as a means to investigate oxidative stress in reperfused hearts. We compared the metabolic and functional consequences of an oxidant load in control rabbit hearts and in hearts reperfused after 30 min of normothermic total ischemia. In controls, H2O2 infusion (H2O2; 5-30 microM) induced a dose-dependent stimulation of GSSG release and a progressive impairment of cardiac function. At these doses, H2O2 challenge of postischemic hearts resulted in biochemical and functional changes identical to those observed in controls. Release of lactate dehydrogenase (LDH) and of GSH was negligible, similar in both groups. In additional experiments, infusion of H2O2 at a much higher dose (200 microM) elicited a further increase in GSSG release from both groups, although GSSG concentrations were lower in postischemic hearts. The functional effects of the 200 microM H2O2 infusion were similar in both groups, all hearts showing rapid and irreversible deterioration of function. Occurrence of irreversible cell injury was also manifested by a large release of LDH and GSH to a similar extent in both groups. These data demonstrate that cardiac tolerance toward oxidants is largely unaffected by a relatively brief episode of severe ischemia and indicate that GSSG release can be reliably used to investigate oxidative stress in reperfused hearts.
Thyroid function modulates beta-adrenergic sensitivity through the regulation of beta-adrenoceptor density. In particular, thyroidectomy decreases and thyroid hormone injections increase beta-adrenoceptor density on human lymphocytes. In the present paper the relationship between receptor modifications and thyroid hormone levels has been studied in human lymphocytes from patients after thyroidectomy. The patterns of early changes as well as recovery trends have been investigated. Results show a statistically significant fall in receptor density, parallelled by a decrease in T3 levels, 1-3 days after thyroidectomy. Recovery of receptor density is observed 5-8 days after surgical intervention and is accompanied by increased T3 levels. There is a positive correlation between receptor density and T3 levels. On the contrary, no statistically significant correlation was observed for receptor density and T4 levels. The time course of disappearance and recovery of receptor density and that of T3 levels have also been analyzed with the aid of a mathematical model fitting experimental data. On this basis, the hypothesis that both down-regulation and subsequent recovery of beta-adrenoceptor density are driven by the fall and rise of T3 is suggested. Data are also discussed in relation to experimental results we have obtained in animal studies.
It has previously been demonstrated that thymus exerts a regulatory influence on beta-adrenergic system during aging. In particular, it has been shown that thymus can correct the beta-adrenoceptor density decrease in old mice. In the present paper results of experiments are reported dealing with the influence of the thymus on alpha-adrenoceptors of mouse brain cortex. Both subtypes of alpha-adrenoceptors are studied separately, using different labelled ligands. Results show that alpha 1-adrenoceptor density decreases in old animals, while alpha 2-adrenoceptor density does not change significantly. A neonatal thymus grafted into old recipients is capable of correcting the alteration observed in old mice. The differential impairment of alpha-adrenoceptors resembles that one previously observed on beta-adrenoceptors, where beta 1-type decreases in number during aging with a parallel decrease of adenylyl-cyclase activity, while beta 2-type remains unchanged.
In order to detect subclinical levels of Doxorubicin (D) cardiotoxicity, 21 patients aged 42 +/- 8 years with malignancies and treated with D as a part of a multiple regimen, were evaluated. The mean cumulative dose of D was 242 +/- 112 mg.m-2 (150 to 520 mg.m-2). Patients with systemic hypertension, valvular diseases, suspected coronary artery disease, ejection fraction less than 55% as assessed by radionuclide angiography, and aged more than 50 years were excluded from the study. A Doppler echocardiographic examination was performed before and after the course of D therapy with a mean interval of 142 days. The following variables were assessed: fractional shortening (FS), ejection fraction (EF), stroke volume (SV), isovolumic relaxation time (IVRT), maximal early diastolic flow velocity (Emax), maximal late diastolic flow velocity (Amax), and mitral deceleration time (Mdt). Indices derived from 19 aged-matched normal subjects were compared to those of the patients before the course of therapy. Doppler echocardiographic measurements did not differ significantly between the control group and patients before the course of therapy. While there were no significant changes in FS, EF, and SV in the study group before and after therapy, indices of diastolic filling showed striking differences: IVRT changed from 72 +/- 11 to 87 +/- 19 ms (P less than 0.001), Emax from 81 +/- 12 to 65 +/- 17 cm.s-1 (P less than 0.001), Mdt from 174 +/- 25 to 183 +/- 34 ms (P less than 0.05), Amax from 44 +/- 17 to 52 +/- 16 cm.s-1 (P less than 0.01). These data demonstrate impaired diastolic filling after doxorubicin therapy at conventional dosages.
The present retrospective analysis reports two studies. In Study 1, clinical aspects of aphasia are compared in right-handed (RH) and non-right-handed (NRH) patients; in Study 2, recovery from aphasia is compared in RH and NRH aphasic patients with a minimum of 5 months of daily language rehabilitation. From a continuous series of 1200 brain-damaged subjects, 24 NRH patients with a vascular lesion documented by computerized tomography were selected. In 19 cases the lesion was in the left hemisphere and in 5 cases in the right hemisphere. For 14 NRH patients, a RH subject with similar lesion, matched for age, education, length of illness, etiology (ischemic vs. hemorrhagic), and, when possible, sex was found. Presence and type of aphasia were compared in the two patients of the same pair and were found similar except for Pair 14; the RH subject had global aphasia and the NRH had conduction-like aphasia. Fifteen NRH patients were rehabilitated and reexamined at least 5 months after the first examination. Recovery of the 12 patients with a left-hemisphere lesion was compared with recovery of a group of RH subjects and no significant differences were found. Recovery of the three patients with right-hemisphere lesions is described. It is concluded that differences in type of aphasia and recovery between RHs and NRHs have been overemphasized in the past and must be reconsidered.
We compared the performance on test of language, apraxia, acalculia and intelligence of 32 children--age 5 to 16 years--and 31 adults, seen at our Aphasia Unit for the sequelae of a brain trauma. Logorrhea was never present among children who had nonfluent aphasia more frequently than adults. Apraxia and acalculia were equally present in the two groups. Twelve children and 15 adults of the first study were retested at variable distance from trauma. No group difference was found in the recovery of auditory comprehension (Token Test) or oral expression (oral confrontation naming and telling-of-an-event). On a battery of verbal and spatial memory tests 6 of the 12 children had pathological scores in one or more tests. Scholastic achievements were compared with those of the nearest kin. We conclude that while aphasia profiles are different in children and adults, the incidence of apraxia and acalculia and the recovery rate do not discriminate the two groups.
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We report two female patients who became global aphasic following a large left hemisphere lesion. With passage of time they recovered to a considerable extent, but three years and six months, respectively, after the former CVA, a new stroke lateralized to the right hemisphere occurred and they showed a definite worsening of language disturbances. Possibilities and limits of the right hemisphere in "taking over" language functions are discussed.
The neuropsychological outcome of 43 patients operated for ACoA aneurysms was assessed with a battery of 15 tests, tapping a wide spectrum of cognitive abilities. As a group ACoA aneurysms patients were impaired on 8 tests, including the three assessing memory. When however, patients falling below the cut-off point determined in normal controls were considered, 42% of the sample was unimpaired and only 35% fell on two or more tests. The analysis of single cases showed that memory was often affected, but short-term memory even more than long-term memory. In addition to the well known memory disorder, the patients showed a wide range of neuropsychological defects, including language and space functions. The hypotheses that could account for this broad-based neuropsychological impairment are discussed.
This study assessed with a neuropsychological battery the outcome of 27 patients operated on for an aneurysm of the Middle Cerebral Artery a mean of 35 months before, and of 27 patients operated for aneurysms of the Posterior Communicating Artery, a mean of 47 months before. Both groups showed a defective pattern of performance that was related to the hemispheric side of the aneurysm with left-sided patients impaired on naming, verbal fluency and verbal short-term memory and right sided patients on both short-term and long-term spatial memory and discrimination of line orientation. In single cases, the scope of neuropsychological impairment was sometimes wider than that expected only on the basis of the competence of the affected hemisphere.
One hundred and fourteen patients operated on for an intracranial aneurysm were followed up in order to investigate their neuropsychological outcome and to detect if there were any clinical features assessed around the time of operation that had prognostic significance. The neuropsychological examination evaluated language, apraxia, memory, intelligence and spatial ability. In the statistical analysis the overall severity of neuropsychological disorder was studied. "Late surgery timing" had a negative influence upon the neuropsychological outcome. There was not a difference between different aneurysm sites. Several patients with an apparently good clinical outcome showed neuropsychological deficits. Neuropsychological assessment is important in the evaluation of outcome after subarachnoid haemorrhage.
Simple reaction time to lateralized visual dot stimuli was studied in 10 fluent and 10 nonfluent right-handed chronic aphasics with left hemisphere lesions. As well as the standard simple reaction time condition, the patients were given a concomitant verbal task, requiring overt articulation while reacting to the visual stimuli. Compared with the control condition, in both aphasic groups the verbal task produced an overall lengthening of latencies, with a significant slowing down of responses to the stimuli located in the right visual half-field. According to these results the verbal concurrent activity appears to involve the left hemisphere as in normal subjects, suggesting that the undamaged regions of the left hemisphere have a role to play in the motor programming of aphasic speech. As a collateral finding, the difference between latencies to stimuli ipsilateral and contralateral to the responding hand--a measure of interhemispheric transmission time--is greatly increased in patients with motor deficits. This is consistent with the view that, in simple visuo-motor reaction time, interhemispheric transfer takes place between anterior regions of the brain.
A patient is described with a 5 year progressive defect of naming and auditory verbal comprehension, the pathological nature of which was presumably degenerative. The auditory comprehension defect unevenly affected different semantic categories, and was particularly severe for the names of animals, fruits and vegetables. The patients showed loss of the verbal knowledge of the physical attributes of the concepts corresponding to the words he was unable to understand, and sparing of the verbal knowledge of the functional attributes. His performance was defective also on the colour-figure and sound-picture matching test.
From April 1981 to May 1984, 23 patients with advanced non-Hodgkin's lymphomas were treated with CEOP (cyclophosphamide, epirubicin, vincristine, and prednisone) or OEPP (vincristine, epirubicin, procarbazine, and prednisone) combination chemotherapy. CR was achieved in 58% and PR in 31% of the patients, giving an overall response rate of 89%. Nine of 15 (60%) previously untreated patients with unfavorable histology obtained a CR and 5 a PR. Median relapse-free survival was 33 months; median overall survival has not yet been reached, and the probability of survival for CRs was 91% after 54 months of follow-up. Acute toxicity was quite acceptable, and chronic cardiac toxicity was detected in 6 patients only. In conclusion, epirubicin used in combination chemotherapies induced durable remissions and prolonged survivals in advanced non-Hodgkin's lymphomas.
In this study we investigated the relationship between deep-seated lesions of the left hemisphere and the aphasic disturbances. Thirty-seven vascular patients with CT-scan, language and neuropsychological examination carried out between 15 and 60 days post-onset were studied. Presence and frequency of apraxic disorders and acalculia are also reported. A consistent relationship between the site of the lesion and the pattern of aphasic disturbances could not be established. The most striking finding was a dissociation between oral and written expression, the latter being disproportionately impaired in a number of subjects.
In this study we investigated whether there are predictors for recovery from ideomotor apraxia (IMA) in patients with focal left hemisphere vascular lesions. Recovery was followed in 26 patients, first examined between 15 and 30 days postonset. They were apraxic at the first examination and had a second (and in some cases, a third) neuropsychological assessment after some months. Six patients with bilateral lesions were also studied to help to define the role of the right hemisphere in recovery from IMA. Other neuropsychological variables (Token Test, Progressive Matrices and Oral Apraxia scores) and site and size of the lesion were also determined. The main results are that improvement from IMA is related to the site of the lesion (anterior lesions faring better); the evolution of IMA is related more to the evolution of oral apraxia than to the evolution of other neuropsychological variables; and the presence of a second lesion in the right hemisphere did not have the negative influence on recovery that might have been expected.