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Biomedical subjects

L Spinelli

Publications and source records attributed to L Spinelli.

At least 55 records · Page 3Linked to original sources

May age onset be relevant in the occurrence of left ventricular hypertrophy in Friedreich's ataxia?

BACKGROUND: Although heart involvement has been widely reported in Friedreich's ataxia (FA), which is the most prevalent of the spino-cerebellar degenerative diseases, the reason that cardiac abnormalities develop has not been yet established. HYPOTHESIS: The investigation was undertaken to study the prevalence and characteristics of cardiac abnormalities in patients with FA and to evaluate whether the presence of left ventricular hypertrophy could be predicted. METHODS: In all, 75 patients with FA and 16 patients with late onset FA (LOFA) disease were investigated for cardiac abnormalities using noninvasive methods. RESULTS: A significant (p < 0.01) difference in the age onset (9.8 +/- 3.9 years) was found in 31 of the 75 patients with FA (41%) who showed left ventricular hypertrophy (LVH) at echocardiographic examination compared with the remaining 44 patients with FA without LVH (12.6 +/- 4.3 years). Moreover, none of the 16 patients with LOFA (age onset 26.5 +/- 4.2 years) showed abnormalities at echocardiographic examination. A significant (p < 0.01) concordance in the familial distribution of hypertrophy was also found. CONCLUSION: These data suggest that the earlier the disease develops the more frequently LVH occurs.

Adolescent↗

Extracranial localization of intracranial interictal epileptiform activity using LORETA (low resolution electromagnetic tomography).

Besides the standard clinical methods of EEG waveshape analysis, mathematical models for reconstruction of dipolar sources from the digitized surface EEG have been introduced in epilepsy research. Although useful for localizing focal sources, these methods are inadequate for analyzing widespread epileptiform activity. A recently introduced alternative method called LORETA (low resolution electromagnetic tomography, Pascual-Marqui et al., 1994), directly computes the current distribution throughout the full brain volume, assuming that neighboring neuronal populations are simultaneously and synchronously activated. In mathematical terms the method selects the smoothest of all possible 3-dimensional current distributions, inherently introducing a certain amount of dispersion. In 7 patients, undergoing simultaneous EEG recording from 10 intracranial (subdural) and 22 extracranial electrodes, 111 subdural discharges (61 subtemporal and 50 lateral temporal) were identified. The exact time point of maximal intracranial activity was automatically identified, and the LORETA solution at that timepoint was computed from the surface EEG. Statistical comparison revealed significantly higher LORETA current density in the area corresponding to the subdurally recorded spike compared to other areas, and a more anterior and more medial LORETA location for subtemporal compared to lateral temporal spikes. This study indicates that the LORETA technique may become a useful method to localize electrical activity in the brain.

Adolescent↗

Relation between diastolic perfusion time and coronary artery stenosis during stress-induced myocardial ischemia.

BACKGROUND: Experimental studies have demonstrated that during stress-induced myocardial ischemia, coronary obstruction and diastolic perfusion time are factors that limit subendocardial perfusion and correlate to degree of myocardial dysfunction. The relation between these two factors has not yet been investigated in humans. The aim of the present study was to assess the relation between diastolic perfusion time and degree of coronary stenosis during different types of stress tests. METHODS AND RESULTS: Nine patients with isolated and proximal stenosis of the left anterior descending coronary artery were selected. Patients underwent three different randomized stress tests (upright, supine bicycle stress test, and transesophageal atrial pacing). Diastolic perfusion time, heart rate (RR interval), and systolic and diastolic pressures were measured during the test and at the ischemic threshold (0.1-mV ST-segment depression). Angiographic measurements of coronary stenosis were evaluated by quantitative coronary angiography. At the ischemic threshold, significant differences among tests were found in heart rate (P < .05), systolic pressure (P < .001), and diastolic pressure (P < .05). In each stress test, diastolic perfusion time at the ischemic threshold was closely correlated with minimal stenosis diameter (r = .97; P < .001) and percent diameter stenosis (r = .92; P < .001) with no difference among the tests. In contrast, heart rate, rate-pressure product, and time to ischemic threshold were not significantly correlated with percent diameter stenosis and minimal stenosis diameter. No significant correlation was observed at the ischemic threshold between diastolic perfusion time and corresponding values of heart rate, despite the close correlation at rest (r = .95; P < .001). CONCLUSIONS: Despite differences in associated hemodynamic responses to various stress tests, a close relation exists between stenosis severity and diastolic perfusion time at the onset of stress-induced myocardial ischemia. Therefore, diastolic perfusion time at the ischemic threshold may be an indirect estimate of the hemodynamic significance of coronary stenosis.

Coronary Angiography↗

Developmental genetical analysis and molecular cloning of the abnormal oocyte gene of Drosophila melanogaster.

Studies of the abnormal oocyte (abo) gene of Drosophila melanogaster have previously been limited to the analysis of a single mutant allele, abnormal oocyte1 (abo1). The abo1 mutation causes a maternal-effect lethality that can be partially rescued zygotically by the abo+ allele and by increasing the dosage of specific regions of heterochromatin denoted ABO. This report describes the properties of abo2, a new P-element-induced allele that allowed us to reexamine the nature of maternal-effect defect. Comparisons of the phenotype of progeny of abo1/abo1 and abo1/abo2 females show that the preblastoderm lethality previously described as a component of the abo mutant maternal effect results from a recessive fertilization defect associated with the abo1 chromosome. We demonstrate here that the abo-induced maternal effect lethality occurs predominately late in embryogenesis after cuticle deposition but before hatching. The phenocritical period for zygotic rescue by heterochromatin coincides with this period of late embryogenesis. We have used the abo2 mutation to map and molecularly clone the gene. We show that the abo gene is located in the 32C cytogenetic interval and identify the putative abo transcript from mRNA isolated from adult females. Using germline transformation, we show that a 9-kb genomic fragment to which the transcript maps, partially fulfills requirement for maternal and zygotic abo+ function.

Animals↗

Interaction systems between heterochromatin and euchromatin in Drosophila melanogaster.

The constitutive heterochromatin is still one of the major unsolved problems in genetics. In Drosophila melanogaster three genetic systems involving specific interactions between heterochromatic and euchromatic genetic elements are known: the Segregation Distortion, the crystal-Stellate and the abo-ABO systems. The genetic and molecular analysis of each system will allow the identification of all the components and the elucidation of the mechanisms underlying their interactions. The results of this analysis should provide insights into the biological significance of heterochromatin and into the evolutionary forces that result in the maintainance and stability of this enigmatic genetic material.

Animals↗

[Physical training of patients with ischemic heart disease. Effects on diastolic time].

In patients (pt) with coronary artery disease diastolic duration is an important determinant of myocardial oxygen supply. To assess the effects of physical training on diastolic duration, twelve male pt with previous infarction were studied. During 12 month training program the physical exercise was of progressively increasing intensity, duration and frequency. Training induced a significant reduction in heart rate. Both systolic and diastolic blood pressure were unchanged. The mean values of electromechanical systole were lower after training. On the contrary, the training induced a lengthening of diastolic duration expressed as percentage of cardiac cycle (% diastole) from 51.4 +/- 2.6 to 57.5 +/- 3.8% (p < 0.001). Thus, this results validate the hypothesis that physical exercise training can improve myocardial perfusion through an increase in diastolic duration, partially independent of bradycardia.

Coronary Disease↗

Site of myocardial ischemia as a determinant of postexercise blood pressure and heart rate response in coronary artery disease.

Forty patients with coronary artery disease and 15 normal subjects (group C) were studied to assess the influence of the site of stress-induced myocardial ischemia on cardiovascular response after exercise. Patients were divided in 2 groups according to myocardial thallium-201 scintigraphy: those with an anteroseptal reversible perfusion defect (group A; n = 24), and those with an inferoposterior reversible perfusion defect (group I; n = 16). All patients underwent serial bicycle exercise stress tests. The first 2 stress tests were interrupted when 0.1 mV of ST-segment depression was achieved (2,000 to 2,500 kg-m); a third test was stopped before the onset of ischemia (1,500 kg-m). Normal subjects performed stress tests at comparable work loads. At ischemic threshold, there was no difference in ejection fraction between groups A (65.5%) and I (67.3%). Mean values and recovery ratios of heart rate and systolic blood pressure were significantly higher in group A than in C and I during the recovery period of the 2,000 to 2,500 kg-m stress test. In contrast, no significant difference was observed among the groups in the 1,500 kg-m stress test, and between groups I and C in any stress test. The data show that in patients with the same degree of stress-induced impairment of ventricular function, the anterior site of ischemia leads to persistently higher values of heart rate and blood pressure after exercise, which are likely due to an enhanced adrenergic discharge.

Blood Pressure↗

Diastolic perfusion time and exercise posture in coronary artery disease patients: correlation with ST segment changes.

The relationship between either heart rate or diastolic time and ST segment depression has been evaluated during supine and upright exercise in 16 coronary artery disease patients. Diastolic perfusion time and ST segment depression were related by a linear regression, which was independent of exercise posture. The entity of ST segment depression was greater during supine than in upright exercise for the same heart rate. The assessment of the relationship between heart rate and diastolic perfusion time during two exercises showed that at the same heart rate, diastolic perfusion time was shorter in supine posture. In conclusion, the greater entity of ST segment depression induced by supine rather than upright exercise might be explained by the effect of supine posture on diastolic perfusion time.

Coronary Disease↗

Method for kinetic analysis of drug-induced cell cycle perturbations.

A method is described for quantitative study of the flux of cells through the cell cycle phases in in vitro systems perturbed by chemicals, such as chemotherapeutic agents. The method utilizes cell count and the flow cytometric technique of bromodeoxyuridine (BrdUrd) labeling, according to an optimized strategy. Cells are exposed to BrdUrd during the last minutes of drug treatment and fixed for analysis at 0, 1/3Ts, 2/3Ts, Ts, and Tc + TG1 recovery times, where Ts, TG1, Tc are the mean durations of phases S and G1 and of the whole cycle of control cells. As an example of application of the proposed procedure, a kinetic study of the effect of 1-(2-chloroethyl)-1-nitrosourea (CNU) on the L1210 cell cycle is described. Simple data analysis, requiring only a pocket calculator, showed that cells in phases G1 and G2M at the end of a 1 h treatment with 1 microgram/ml CNU were fully able to leave these phases but were destined to remain blocked in the following G2M phase (G1 for a minority of them). We also found that cells initially in S phase were slightly delayed in completing their S phase and that 50% of them remained temporarily blocked in the subsequent G2M phase, irrespective of their position in the S phase.

Animals↗

Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer.

We quantified and examined the kinetics of DNA interstrand cross links (DNA-ISC) caused by Cis dichlorodiammine platinum (DDP) using the method of alkaline elution in 58 highly purified human ovarian tumours growing in primary culture. A large heterogeneity in both the quantity and kinetics of DDP induced DNA-ISC was observed in cultures derived from neoplasms of different patients and from different lesions of the same patient. In the majority of cases. DNA-ISC lasted for prolonged time intervals after 1 h drug exposure, being significantly repaired only 48 or 72 h following drug washout. The persistence of DNA-ISC is probably due to a prolonged formation of these lesions for up to 24 h as assessed by the change in the repair kinetics that occurred after preventing new DNA-ISC formation by quenching of monoadducts with thiourea. The inefficient repair of DDP monoadducts appears therefore to be a possible reason for the permanence of DNA-ISC. These studies suggest that the long permanence of DNA-ISC in human ovarian cancer could be the basis for the high selectivity of DDP for this human malignancy.

Cisplatin↗

Diastolic perfusion time at ischemic threshold in patients with stress-induced ischemia.

BACKGROUND: To evaluate the relevance of diastolic perfusion time on the mechanisms underlying stress-induced ischemia, 16 patients with coronary artery disease and seven patients with syndrome X underwent five randomized stress tests (upright and supine exercise with and without therapy, transesophageal atrial pacing). METHODS AND RESULTS: Exercise duration Time to 0.1 mV ST segment depression, heart rate, rate-pressure product, and diastolic perfusion time were evaluated for each patient during stress tests. In both groups, variability coefficients of the above-mentioned parameters were not different at rest. At ischemic threshold (0.1 mV ST segment depression) in patients with coronary artery disease, the variability coefficient of exercise duration (40.1 +/- 22.2) was significantly higher (p less than 0.0001) than those of heart rate (12.8 +/- 2.9), rate-pressure product (14.8 +/- 3.3), and diastolic perfusion time (0.39 +/- 0.1). The variability coefficient of diastolic perfusion time was also significantly (p less than 0.0001) lower than those of heart rate and rate-pressure product. Similarly, the variability coefficient of diastolic perfusion time (0.44 +/- 0.1) in syndrome X patients was significantly lower (p less than 0.0001) than those of exercise duration (28.2 +/- 9.4), heart rate (12 +/- 1.4), and rate-pressure product (14.6 +/- 1.3). CONCLUSIONS: Fixed diastolic perfusion time at ischemic threshold, despite different kinds of stress tests and variability of heart rate and rate-pressure product, indicates the relevant role of diastolic perfusion time in determining myocardial ischemia.

Adult↗

Diastolic time at ischemic threshold in patients with syndrome X.

The patients with so-called syndrome X experience true myocardial ischaemia in spite of their anatomically normal coronary arteries. The pathogenetic mechanism of the effort-induced ischaemia in these patients should be obviously different from that of patients with atherosclerotic coronary artery lesions. An inadequate coronary dilatory capacity in response to increased oxygen demand has been proposed as mechanism responsible of ischaemic response to effort (Canon et al., 1983; Canon et al., 1985). Since diastolic duration expressed as percentage of the cardiac cycle has implications with the myocardial oxygen demand/supply ratio (Boudoulas et al., 1982; Maseri et al., 1977), the purpose of this study has been to evaluate the behaviour of this parameter at the outcome of the ischaemic electrocardiographic changes during stress testing in the patients with syndrome X.

Adult↗

Exercise-induced impairment of diastolic time in patients with X syndrome.

Since an abnormal shortening of diastolic duration during exercise in the patients with coronary artery disease was demonstrated, time course of diastolic period (cardiac cycle minus electromechanical systole) calculated from polycardiographic recording has been assessed in patients with X syndrome and in normal age-matched subjects during supine ergometer exercise. All patients with X syndrome had positive exercise stress response (more than 0.1 mV of ST segment depression). Duration of diastole expressed as percent of cardiac cycle was significantly shorter at the intermediate steps and at the peak of exercise in patients with X syndrome compared with normal subjects (p less than 0.05). When the relationship between heart rate and diastolic time was examined, an inverse nonlinear regression was found both in normal subjects and in patients with X syndrome. The exercise values of diastolic time observed in patients with X syndrome were significantly shorter than those predicted as normal diastolic time heart rate relation. Thus the patients with X syndrome demonstrated abnormalities in the decrement of diastolic time with exercise. We hypothesized that this disproportionate shortening, by reducing subendocardial blood flow, might induce a worsening of ischemic response to exercise.

Angina Pectoris↗