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Biomedical subjects

Luigi Murri

Publications and source records attributed to Luigi Murri.

At least 37 records · Page 2Linked to original sources

Lactate production and catecholamine profile during aerobic exercise in normotensive OSAS patients.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the catecholaminergic activity and lactate concentration during exercise in normotensive patients with obstructive sleep apnoea syndrome (OSAS). PATIENTS AND METHODS: Thirteen normotensive patients affected by OSAS (mean age+/-standard error (SE), 52.6+/-2.8 yrs; mean apnoea-hypopnea index, 35.7+/-20.3) were enrolled in the study. Night-polysomnography and multiple sleep latency test in the sleep laboratory were performed for every patient. Patients also underwent an incremental workload exercise on a cycloergometer. We evaluated plasma epinephrine and norepinephrine levels in aerobic exercise conditions, relating them to lactate levels. RESULTS: Analysis of the venous lactate curve showed that exercise lactate levels were significantly higher (peak normalised levels, 782 vs. 270%; P<0.001 ), and an earlier lactate threshold was detected, in the patients compared to normal controls. While plasma catecholamine levels were abnormally high in almost all patients at rest, exercise values were not significantly different from controls. Lactate/norepinephrine and lactate/epinephrine area ratios were significantly higher in OSAS subjects than in controls (2.25 vs. 1.21 and 2.37 vs. 1.03, respectively). CONCLUSIONS: The results indicate that abnormal production of lactate during exercise occurs in OSAS, possibly due to some muscular metabolic modification. While catecholaminergic activity is abnormally increased at rest, this activity does not seem to play a significant role in lactate concentration during exercise in these patients.

Blood Pressure↗

A general automatic method for the analysis of NREM sleep microstructure.

OBJECTIVE: To define a unified method for the automatic recognition and quantitative description of EEG phasic events of sleep microstructure occurring during NREM sleep, particularly arousals, phase A subtypes of cyclic alternating pattern and spindles. METHODS: The NREM sleep EEG of 10 normal young subjects was examined in order to recognize formal phasic events of sleep microstructure. The following 'formal' events (i.e. events defined exclusively on the basis of automatic analysis criteria) were classified: arousals, A1-phases (A-phases not including arousals) and A2- and A3-phases (A-phases including arousals). Spindle bursts, corresponding to visually recognized spindles, were also formally defined. The identification of these events was carried out following a three-step procedure: (1) computation of band-related descriptors derived from the EEG signal, (2) introduction of suitable thresholds and (3) application of simple logical principles, i.e. an exclusion principle and an overlapping principle. RESULTS: Formal A-phases, arousals and spindle bursts showed spectral characteristics which were consistent with visual inspection. The value of the parameter Correctness for the recognition of the A-phases was 83.5%. In particular, the different physiological distribution of the A-phases in Stage 2 preceding slow wave sleep with respect to Stage 2 preceding REM sleep was confirmed. CONCLUSIONS: The proposed method provides a unified quantitative approach to the study of sleep microstructure. Visually defined events can be reliably identified by means of automatic recognition.

Adult↗

Seizures induced by nursery rhymes and children's games.

We report the case of a 20 years aged male patient with seizures induced by nursery rhymes and children's games. Seizures were precipitated by various triggers, including thinking to a children's rhyme, to a children's game, to the action of giving a kiss with a hand. Among the above triggers, only the last one was able to induce a seizure during our observation, characterised by jerking of the upper limbs and loss of consciousness with a quick recovery. The electroclinical features were of a brief paroxysm and diffuse theta/delta activity on electroencephalogram, with frontal maximal expression. The playful aspect and the reference to childhood intrinsically associated with an emotional component seem to be the true feature all the stimuli have in common and therefore this form could be classified as an emotional one. To our knowledge seizures precipitated by these kind of stimuli have never before been reported.

Adult↗

Daytime sleepiness in epilepsy patients receiving topiramate monotherapy.

PURPOSE: Limited research has focused to date on objective neurophysiological evaluation of daytime sleepiness in patients treated with newer antiepileptic drugs (AEDs), especially when used as monotherapy. This study was aimed at assessing occurrence of daytime sleepiness in newly diagnosed, drug-naïve patients with partial epilepsy receiving initial topiramate (TPM) monotherapy. METHODS: Daytime vigilance was assessed in 14 consecutive, newly diagnosed and never medicated adult patients with focal epilepsy, receiving monotherapy with TPM. At baseline and 2 months after slowly titrated therapy with TPM, 200 mg/day, patients underwent the Multiple Sleep Latency Test (MSLT), visual simple and choice reaction times (VRT), and self-rated their own degree of sleepiness with the Epworth Sleepiness Scale. A group of 14 age- and gender-matched healthy volunteers served as controls. RESULTS: At baseline, mean daytime sleep latencies on the MSLT were comparable in patients and in controls. Two months after TPM monotherapy, MSLT scores did not significantly change in patients as compared with pretreatment values. Accordingly, subjective daytime sleepiness and VRTs, which were comparable in controls and in untreated patients at baseline, did not change in patients after TPM monotherapy. CONCLUSIONS: Study results suggest that an initial short-course monotherapy with TPM, 200 mg/day, does not impair daytime vigilance in newly diagnosed adult patients with partial seizures.

Adult↗

Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation.

Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline (t(0)), 1 month (t(1), short-term VNS) and 36 months after VNS initiation (t(2), long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed.Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean+/-S.D.: 40+/-18 normalized units (nu) at t(0), 38+/-17 nu at t(1), 18+/-10 nu at t(2); p<0.05 of t(2) vs. either t(0) or t(1)). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16+/-13 nu at t(0) and +15+/-8 nu at t(1) vs. +3+/-13 nu at t(2), p<0.02; HF day-to-night change: -18+/-13 nu at t(0) and -13+/-11 nu at t(1) vs. +3+/-12 nu at t(2), p<0.003). No significant changes were observed with regard to the time-domain parameters of the heart rate variability. Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of >50%, two patients of <50% and one had no changes in his seizure frequency. Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.

Adult↗

Decreased platelet cytochrome c oxidase activity is accompanied by increased blood lactate concentration during exercise in patients with Alzheimer disease.

Increasing evidence indicates that mitochondrial dysfunction occurs in the central nervous system as well as in the peripheral tissues from Alzheimer's disease (AD) patients. We have recently shown that mitochondrial cytochrome c oxidase (COX) activity is significantly reduced in brain and platelets from AD patients compared to controls. In the present study we investigated whether impaired COX activity could have functional consequences on energy metabolism. Blood lactate concentration was monitored at rest and during incremental exercise in 22 AD patients in whom COX activity in platelets was decreased compared to controls (35.7 +/- 11.4 vs 48.4 +/- 1.4 nmol/min/mg, P < 0.01). In both resting and exercising conditions, blood lactate was significantly higher in AD patients than in controls. Although the magnitude of exercise-related lactate accumulation was not different between the two groups, an anticipated anaerobic lactate threshold during the incremental forearm exercise was found in AD patients (50% of maximal voluntary contraction MVC compared to 60% in controls). COX activity was inversely related to lactate at a significant level for resting condition (r = -0.65) and borderline for anaerobic threshold exercise level. These results support the hypothesis of a systemic impairment of the mitochondrial function in AD and indicate that decreased COX activity could have functional consequences on metabolism.

Aged↗

Daytime vigilance and quality of life in epileptic patients treated with vagus nerve stimulation.

OBJECTIVES: The goal of this study was to determine if vagus nerve stimulation (VNS) has any effect on daytime vigilance and perceived sense of well-being. METHODS: Multiple Sleep Latency Tests (MSLTs) were performed and visual reaction times (VRTs) obtained in eight epileptic patients before and during treatment with VNS. Prior to VNS initiation patients' baseline MSLT and VRT scores were recorded. Six months after VNS was initiated, treatment MSLT and VRT scores were obtained. A group of 12 age-matched healthy subjects served as controls. In addition, there was a global evaluation of well-being at baseline and during a follow-up of 6 months. RESULTS: As expected, patients evaluated both at baseline and during VNS showed more sleepiness than controls. In this group, baseline sleep latencies on the MSLT were significantly shorter, while VRT latencies were significantly longer than those of controls. After 6 months of VNS, MSLT scores in the eight patients did not change significantly with respect to baseline. However, if the single patient treated with relatively high stimulus intensities (1.75 mA) was excluded from the group and only the seven patients treated with low stimulus intensities (<or=1.5 mA) were considered, a significant effect of chronic VNS on MSLT scores could be observed. In fact, the mean sleep latency (MSL) average of the seven subjects significantly improved from 9.9+/-2.5 minutes during baseline to 10.9+/-2.3 minutes after 6 months of VNS (P<0.05). Conversely, the only patient treated with high stimulus intensities showed increased sleepiness, with MSL decreasing from 14.4 to 9.8 minutes. On the other hand, VRT latencies did not significantly change during VNS. Patients considered as a whole had significant improvements on global evaluation scores of quality of life. CONCLUSION: VNS at low stimulus intensities promotes daytime vigilance in adult epileptic patients and has a positive effect on quality of life.

Adult↗

Prevalence of stroke and transient ischaemic attack in the elderly population of an Italian rural community.

OBJECTIVES: To evaluate the prevalence of stroke and transient ischaemic attack in the elderly population, including the oldest residents, of a rural Italian community. METHODS: A door-to-door survey was performed between April and October 2001 in 2390 subjects aged 65 years and over. A symptom questionnaire validated by medical records and neurological examination was employed. RESULTS: Complete information was available for 2260 subjects. The overall prevalence of stroke was 8.2% in males and 5.1% in females. In the very elderly, this increased to 10.7% in males and 10% in females and decreased only in males aged 90 years or over. The overall prevalence of transient ischaemic attack was 7% in males and 4.9% in females. This, too, increased with age, reaching 10.2% in males and 7.4% in females and decreased only in subjects of both sexes aged 85 years or over. CONCLUSIONS: An actual estimate of the high prevalence of cerebrovascular disease in the elderly population, even in very old subjects, was thus achieved. Appropriate health care services consequently need to be planned.

Age Distribution↗

A damage to locus coeruleus neurons converts sporadic seizures into self-sustaining limbic status epilepticus.

Various studies demonstrated that the neurotransmitter norepinephrine (NE) plays a relevant role in modulating seizures; in particular, a powerful effect consists in delaying the kindling of limbic areas such as the amygdala and hippocampus. Given the rich NE innervation of limbic regions, we selected a sensitive trigger area, the anterior piriform cortex, to test whether previous loss of noradrenergic terminals modifies sporadic seizures in rats. The damage to locus coeruleus terminals was produced by using the selective neurotoxin N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 60 mg/kg i.p.). In intact rats, bicuculline (a GABA-A antagonist, 118 pmol) microinfused into this area produced sporadic seizures, while in rats previously injected with DSP-4, bicuculline determined long-lasting self-sustaining status epilepticus. In intact rats, sporadic seizures were accompanied by a marked increase in norepinephrine release in the contralateral piriform cortex, while in locus coeruleus-lesioned rats this phenomenon was attenuated. While bicuculline-induced sporadic seizures were prevented by the focal infusion of amino-7-phosphonoheptanoic acid (AP-7, a selective NMDA antagonist), or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide (NBQX, a selective non-NMDA antagonist), status epilepticus obtained in norepinephrine-lesioned rats was insensitive to AP-7 but was still inhibited by NBQX. By using fluorescent staining for damaged (Fluoro-Jade B) and intact (DAPI) neurons, as well as cresyl violet, we found that rats undergoing status epilepticus developed neuronal loss in various limbic regions. This study demonstrates a powerful effect of noradrenergic terminals in regulating the onset of limbic status epilepticus and its sensitivity to specific glutamate antagonists.

Animals↗

Dopaminergic modulation of visual-spatial working memory in Parkinson's disease.

Visual-spatial working memory (WM) impairment is frequently associated with the early stage of Parkinson's disease (PD). The aim of this study was to evaluate the performance of a group of PD patients in visual-spatial and visual-object WM tasks and to investigate the effect of administering the dopaminergic agonist apomorphine (experiment 1) or the dopamine precursor L-dopa (experiment 2) on the performance of tests assessing these functions. To study WM processes, the PD patients and age-matched normal controls were given an n-back task paradigm. In both experiments, the PD patients were submitted to two evaluations: one after a 12-hour therapy washout and the other 15 min after a subcutaneous infusion of apomorphine (average 0.04 mg/kg) or 20/30 min after L-dopa intake (200 mg p.o.). The apomorphine infusion had a worsening effect on reaction times in both visual-spatial and visual-object WM tasks, but it did not influence performance accuracy. Instead, L-dopa administration had a ameliorative effect on accuracy and reaction times in both visual-spatial and visual-object tasks. These results highlight the role of dopamine in the modulation of the WM function in PD patients.

Apomorphine↗

An automatic method for the recognition and classification of the A-phases of the cyclic alternating pattern.

OBJECTIVES: The aim of this research has been to introduce an automatic method, simple from the mathematical and computational points of view, for the recognition and classification of the A-phases of the cyclic alternating pattern. METHODS: The automatic method was based on the computation of 5 descriptors, which were derived from the EEG signal and were able to provide a meaningful data reduction. Each of them corresponded to a different frequency band. RESULTS: The computation of these descriptors, followed by the introduction of two suitable thresholds and of simple criteria for logical discrimination, provided results which were in good agreement with those obtained with visual analysis. The method was versatile and could be applied to the study of other important microstructure phenomena by means of very small adaptations. CONCLUSIONS: The simplicity of the method leads to a better understanding and a more precise definition of the visual criteria for the recognition and classification of the microstructure phenomena.

Adult↗

Dream recall frequency in epilepsy patients with partial and generalized seizures: a dream diary study.

PURPOSE: The frequency of dream recall (DR) in patients with brain diseases has proved to be indicative of the relation between sleep disturbances and the functioning of cognitive processes during sleep. In this study we attempted to ascertain whether DR frequency in patients with complex partial seizures (CPSs) is higher than that in those with generalized seizures. METHODS: DR frequency was assessed by means of a 60-day dream diary in patients with CPSs, whose epileptic focus was in the right (n = 12) or left temporal lobe (n = 28), and with idiopathic generalized seizures (n = 21). The patients enrolled in the study were not impaired in global cognitive and memory functioning. RESULTS: The ability to recall dreams was established in nearly all patients with either CPSs or generalized seizures. DR frequency resulted significantly higher (about twice) in patients with CPSs, regardless of (a) the side of the epileptic focus, (b) the presence of a cerebral lesion detectable on a computed tomography (CT) scan, or (c) the occurrence of seizures in the previous day. CONCLUSIONS: These findings indicate that overall, DR occurs in medicated epilepsy patients with CPSs more frequently than reported in previous studies. The high DR frequency observed in these patients, regardless of the side of the epileptic focus, is in agreement with the assumption that tempoparietal areas of both hemispheres are involved in the production and recall of the dream experience.

Adult↗

Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients.

BACKGROUND: Although the pathogenic mechanisms of selective loss of motor neurons in amyotrophic lateral sclerosis (ALS) are unknown, there is increasing evidence for the hypothesis of an oxidative stress-related mitochondrial involvement as key determinant of motor neuron degeneration OBJECTIVE: The aim of our study has been to assess blood levels of peroxidation markers and to relate them to in-vivo oxidative metabolism in exercising muscle in patients affected by ALS. METHOD: For this purpose 10 patients (seven men and three women, mean age 58.5 +/- 8.2 SD), performed an incremental bicycling test for the assessment of lipoperoxides and lactate during exercise. RESULTS: At rest, the ALS patients had higher than normal levels of both lactate (2.82 +/- 0.76 mmol/L; normal range: 0.67-2.47 mmol/L) and lipoperoxides (361.7 +/- 40.2 AU; normal range: 250-320 AU), the latter corresponding to a level of moderate oxidative stress. A further increment during exercise was observed both at lactate threshold and maximal power output levels. Values of blood lipoperoxides were significantly higher (P < 0.05) than those in control patients affected by chronic motor denervating processes of different origins and related (P < 0.01) to lactate production on exercising. CONCLUSIONS: These findings indicate the occurrence of an abnormally increased size of blood free radical pool in resting conditions and during exercise in ALS patients. The relationship between the levels of reactive oxygen species and lactate production is indicative of a tight link between mitochondrial function and oxidative stress in ALS.

Aged↗

A screening for superoxide dismutase-1 D90A mutation in Italian patients with sporadic amyotrophic lateral sclerosis.

The Aspartate-90-Alanine (D90A) mutation on SOD-1 gene, the only known change causing recessive familial amyotrophic lateral sclerosis (FALS), is associated with a uniform phenotype characterized by slowly ascending paresis and long survival. Originally reported in Scandinavian cases, it has also been detected in patients from other countries. A common haplotype, probably of Scandinavian origin, has been demonstrated in D90A recessive pedigrees. In this study we screened the SOD-1 gene for the D90A mutation in 56 Italian patients from north-west Tuscany with sporadic ALS in order to evaluate the occurrence of this mutation and its genotype-phenotype correlation in Italy. We found the homozygous D90A mutation in one patient (1.8%), harboring the classical phenotype related to this mutation. No other mutations were detected in any of the five SOD-1 exons in our group. Our results confirm that recessive D90A mutation is present in Italy and it is associated with the phenotype already described A screening for that mutation, easily made by RFLP, should be made in sporadic ALS patients, especially where clinical investigation indicates its presence.

Adult↗

Discordant effect of IFN-beta1a therapy on anti-IFN antibodies and thyroid disease development in patients with multiple sclerosis.

Interferon-beta1b (IFN-beta1b) therapy is associated with a relatively high risk of developing thyroid disease. IFN-beta1a is regarded as less immunogenic than IFN-beta1b because of its structural homology to natural IFN-beta. We assessed the effect of 1 year of IFN-beta1a treatment on thyroid function and autoimmunity in 14 multiple sclerosis (MS) patients. The results were compared with those obtained in a series of 31 MS patients treated with IFN-beta1b. The prevalence of positive binding antibody (BAb) titer and neutralizing (NAb) anti-IFN antibody titer in the two groups was also assessed. The BAb and NAb positivity rate in IFN-beta1a-treated patients was significantly lower than in the group submitted to IFN-beta1b therapy (7% vs. 84% and 0% vs. 30%, respectively). Although the incidence of thyroid dysfunction was slightly higher in IFN-beta1b-treated patients than in those undergoing IFN-beta1a treatment (33% vs. 23%, respectively), it did not reach statistical significance. Thyroid disease was unrelated to the presence of positive serum BAb or NAb titer in both the group undergoing IFN-beta1a therapy and in that treated with IFN-beta1b. In both groups, thyroid disease developed mostly in women (71%) against a background of preexisting thyroiditis and a diffuse hypoechoic ultrasound thyroid pattern (80%). IFN-beta1a treatment was associated with a significantly lower prevalence of both BAb and NAb-positive titers than was IFN-beta1b. Conversely, thyroid disease was similar and unrelated to the presence of positive anti-IFN-beta antibody titer. Therefore, routine thyroid assessment may be advised during IFN-beta1a treatment, especially in patients with preexisting thyroiditis.

Adult↗

Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy.

BACKGROUND: Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding for regulatory proteins of mitochondrial respiratory function, the mitochondrial transcription factor A (h-mtTFA) has been proposed to be a target of thyroid hormone action. The aim of this study has been to relate h-mtTFA levels in the skeletal muscle of patients affected by Hashimoto's hypothyroidism and myopathy (HHM) to muscle disease and thyroid status. PATIENTS AND METHODS: Eleven HHM patients underwent complete thyroid status and neurologic assessment, along with determination of exercise lactate anaerobic threshold (LT) and muscle biopsy in which h-mtTFA levels were measured and mtDNA was analyzed. RESULTS: Decreased exercise lactate threshold, presence of cytochrome c oxidase negative fibers, reduction of cytochrome c oxidase activity, and mitochondrial DNA copy number at muscle biopsy were indicative of mitochondrial involvement in these patients. Furthermore, muscle h-mtTFA levels were reduced to a variable extent in comparison with a group of euthyroid controls. The h-mtTFA levels were inversely correlated with TSH and LT lactate, and positively correlated with FT4. CONCLUSIONS: These results indicate that low levels of the h-mtTFA occur in skeletal muscle of HHM and suggest that abnormal h-mtTFA turnover may be implicated in the pathogenesis of mitochondrial alterations in this disease.

Biopsy↗