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Biomedical subjects

N Locuratolo

Publications and source records attributed to N Locuratolo.

At least 19 recordsLinked to original sources

Abnormal head nociceptive withdrawal reaction to facial nociceptive stimuli in Parkinson's disease.

INTRODUCTION: Trigemino-cervical-spinal reflexes (TCSRs) are complex brainstem stereotyped nociceptive responses involved in a defensive withdrawal reaction of the head from facial nociceptive stimuli. OBJECTIVE: The present study was undertaken to collect data on possible TCSR abnormalities in idiopathic Parkinson's disease (PD) and investigate any correlation with motor signs and L-DOPA administration. METHODS: TCSRs were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the supraorbital nerve in 18 patients with PD and 24 controls. The latency (L) and area (A), as well as the sensory (ST), painful (PT) and reflex (RT) thresholds were measured during the 'off' and 'on' state, and possible correlations with the UPDRS III total score, selected subscores (tremor, neck rigidity, upper limb rigidity, akinesia, rising from a chair, posture and posture instability) and duration of illness were investigated. RESULTS: Significant changes between controls and PD patients were found in the L, A, PT and RT of TCSRs. These results were not significantly influenced by L-DOPA treatment. A significant correlation was found between neck rigidity, postural instability scores and duration of illness and the TCSR L and A values in PD patients in the 'off' state. CONCLUSIONS: TCSRs abnormalities, combined with dopamine resistance, are consistent with a primary loss of brainstem neurons mediating a complex sensory-motor integration including neck muscle tone and postural control as well as the head withdrawal reaction to the nociceptive stimuli. SIGNIFICANCE: TCSRs may represent a useful tool for the assessment of brainstem sensory-motor function in PD as well as other movement and degenerative disorders.

Aged↗

Reversible diffusion MRI abnormalities and transient mutism after liver transplantation.

Transient mutism was observed in a liver transplant patient under immunosuppressant therapy with cyclosporine A and antifungal prophylaxis with amphotericin B. Fluid-attenuated inversion recovery and diffusion-weighted images revealed reversible bilateral symmetric hyperintensity located in the frontal motor cortex and corticospinal tracts. These MRI abnormalities may be caused by acute edema, possibly a combination of cytotoxic and vasogenic edema, which resolved with a prompt change in therapy.

Diffusion Magnetic Resonance Imaging↗

Psychophysiological approach in Parkinson's disease: L-dopa effects on preprogramming and control activity.

To investigate whether preprogramming (Bereitschaftspotential, BP) and control activity (skilled performance positivity, SPP) in a complex task are sensitive to L-dopa, movement related potentials (MRPs) were recorded in 12 non-demented Parkinson's disease (PD) patients before and after acute L-dopa administration, and in 17 control subjects. After L-dopa administration, the PD patients scored a significantly higher percentage of correct performances ( p<0.05), linked to a decreased BP amplitude ( p<0.001) and an increased SPP amplitude ( p<0.005), than before therapy. Our findings suggest that preprogramming activity is impaired in untreated PD patients. Dopaminergic drug administration seems to restore their ability to use more automatic motor strategies which become more similar to that of normal subjects.

Aged↗

Mitochondrial myopathy, parkinsonism, and multiple mtDNA deletions in a Sephardic Jewish family.

The authors describe a family of Sephardic Jews with progressive external ophthalmoparesis, skeletal muscle weakness, and parkinsonism. Autosomal recessive inheritance was suggested by many consanguineous marriages, although a dominant disorder could not be excluded. No linkage to known progressive external ophthalmoparesis locus was found. The presence of cytochrome c oxidase-negative ragged-red fibers, biochemically reduced respiratory chain complexes, and multiple mitochondrial DNA deletions in muscle biopsies from four patients suggested a new mitochondrial disorder of intergenomic communication.

Adult↗

Epidemiology of multiple system atrophy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Multiple system atrophy (MSA) is a form of atypical parkinsonism with unknown etiology. The epidemiological studies conducted up to now on this disease are scarce. The incidence rate is about 0.6 cases per 100,000 persons per year. The prevalence rates show 4-5 cases per 100,000 persons. In Italy, about 4,900 prevalent cases have been estimated. The mean onset age is about 54 years; the median survival is 7-9 years. Only one case-control study has been performed on this disease. This study showed an increased risk of MSA associated with occupational exposure to organic solvents, plastic monomers and additives, pesticides and metals. Smoking habits seem to be less frequent in MSA cases (as in Parkinson's disease cases) than in healthy controls. Quinn's clinical criteria and those of the Consensus Conference promoted by the American Academy of Neurology are in fair agreement. We have performed a case-control study on 73 MSA cases, 146 hospital controls and 73 population controls.

Age of Onset↗

Epidemiology of progressive supranuclear palsy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Progressive supranuclear palsy (PSP) is a rare form of parkinsonism. The incidence rates are about 0.3-1.1 cases per 100,000 persons. The only two case-control studies performed up to now show conflictual results as regards education and residence in rural areas. Recently, a cluster of PSP and atypical parkinsonism has been observed in French Antilles. The hypothesis is that a consumption of both tropical fruit and herbal tea may be associated with PSP onset. Some PSP families with a probably autosomal dominant transmission have been described. A high frequency of a tau haplotype (H1/H1) associated with PSP is reported by some authors. The significance of this association is still not clear. We have performed a case-control study on 58 PSP cases, 116 hospital controls and 58 population controls.

Age of Onset↗

Heart rate variability in Parkinson's disease patients treated with tolcapone.

Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson's disease (PD) patients in chronic Levodopa (L-dopa) therapy. The interaction between tolcapone and the endogenous metabolism of catecholamines points to a possible influence on autonomic cardiovascular function.Cardiovascular reflexes have been analysed in a group of seven PD patients (four males, three females; mean age 69.7years, mean disease duration 14.1years) by means of the heart rate variability (HRV) method using a continuous 24-h ECG (ECGD), before and after six months of treatment with tolcapone (in addition to L-dopa).We have observed no statistically significant differences in HRV parameters, nor any changes in the incidence of hyperkinetic and hypokinetic arrhythmias, which suggest that autonomic cardiovascular function in PD patients is not influenced by six months of treatment with tolcapone.

Journal Article↗

The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronic variant of the disease-associated H1 haplotype in Italian cases.

Mutations in coding exons or exon 10 5'-splice-site of the gene for microtubule-associated protein tau can cause chromosome 17-linked frontotemporal dementia and parkinsonism (FTDP-17). We sequenced the 11 coding exons plus exon-intron boundaries of the tau gene in 15 cases of progressive supranuclear palsy (PSP), and found no mutations in coding exons or exon ten 5'-splice sites. These data indicate that typical PSP is not associated with tau gene mutations similar to those causing FTDP-17. We also observed a +39deltaG base change in the intron following exon 4 in three out of 69 PSP cases (all three Italians), whereas it was not found in 150 Dutch controls and once in 112 Italian controls. The +39deltaG variant arose in the context of the PSP-associated tau H1 haplotype. Although a pathogenic role cannot be entirely excluded, +39deltaG is likely to be a rare polymorphism that may be in linkage disequilibrium with a biologically relevant locus inside or near to the tau gene.

Aged↗

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease.

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.

Aged↗

Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production.

Recent evidence suggests that several growth factors participate in diabetic glomerular disease by mediating increased extracellular matrix accumulation and altered cell growth and turnover leading to mesangial expansion. Transforming growth factor (TGF)-beta has been demonstrated to be upregulated both in vivo and in vitro, whereas studies on the activity of the renal insulin-like growth factor (IGF) system in experimental diabetes have provided conflicting results. We investigated the effects of prolonged exposure (4 weeks) of cultured human and rat mesangial cells to high (30 mmol/l) glucose vs iso-osmolar mannitol or normal (5.5 mmol/l) glucose levels on: 1) the autocrine/paracrine activity of the IGF system (as assessed by measuring IGF-I and II, IGF-I and II receptors, and IGF binding proteins); and, in parallel, on 2) TGF-beta 1 gene expression; 3) matrix production; and 4) cell proliferation. High glucose levels progressively increased the medium content of IGF-I and the mRNA levels for IGF-I and IGF-II, increased IGF-I and IGF-II binding and IGF-I receptor gene expression, and reduced IGF binding protein production. TGF-beta 1 transcripts and matrix accumulation and gene expression were increased in parallel, whereas cell proliferation was reduced. Iso-osmolar mannitol did not affect any of the above parameters. These experiments demonstrated that high glucose levels induce enhanced mesangial IGF activity, together with enhanced TGF-beta 1 gene expression, increased matrix production, and reduced cell proliferation. It is possible that IGFs participate in mediating diabetes-induced changes in matrix turnover leading to mesangial expansion, by acting in a paracrine/autocrine fashion within the glomerulus.

Animals↗

Insulin-like growth factors I and II stimulate extracellular matrix production in human glomerular mesangial cells. Comparison with transforming growth factor-beta.

An enhanced paracrine/autocrine activity of the insulin-like growth factor (IGF) system within the glomerulus has been implicated together with up-regulation of transforming growth factor-beta (TGFbeta) in the pathogenesis of diabetic glomerular disease. This would imply their ability to modulate extracellular matrix (ECM) and cell turnover at the mesangial level, but the direct effects of IGFs on ECM production have not been demonstrated to date. These experiments in cultured human mesangial cells were aimed at assessing the effects of IGF-I and IGF-II, compared with those of TGFbeta, on 1) ECM medium accumulation and gene expression, and 2) total protein synthesis and cell proliferation. Human mesangial cells were grown to subconfluence, growth arrested for 48 h, and then exposed for 4-24 h to serum-free medium containing IGF-I (10(-7) - 10(-11) M), IGF-II (10(-7) - 10(-11) M), TGFbeta (10(-9) - 10(-11) M), or various combinations of two of these growth factors (10(-9)M). All three growth factors dose dependently increased ECM protein and messenger RNA levels. The combination of either IGF-I or IGF-II with TGFbeta, but not the two IGFs together, produced additive effects on matrix production. Total protein synthesis was also increased by IGF-I, IGF-II, and TGFbeta, although to a lesser extent than ECM production, whereas cell proliferation was enhanced by IGFs but not by TGFbeta. These results demonstrate that IGF-I and IGF-II are effective, although less potent than TGFbeta, in stimulating the production of the ECM components that accumulate in the mesangial region during the course of diabetic glomerular disease.

Cell Division↗

Changes in central and peripheral nervous system function during hypoglycemia in man: an electro-physiological quantification.

We measured somatosensory evoked potentials (SEP) in normal subjects during acute (group A) and moderately prolonged (group B) hypoglycemia. We considered the following parameters: peripheral conduction velocity (wrist-Erb CV), conduction time (CT) between brachial plexus and the cervical cord (Erb-N13) and central CT from the cervical cord/lower brainstem lemniscal pathway to the cortex (N13-N20). In group A, the electrophysiological parameters did not change significantly throughout the study. In group B, mean N13-N20 CT increased from a basal values of 5.82 +/- 0.11 to 6.22 +/- 0.11 msec at 105 min (p less than 0.02) and 6.33 +/- 0.11 msec at 120 min (p less than 0.05). This study indicates that neither acute nor moderately prolonged hypoglycemia influence the peripheral nerve function in normal subjects and provides evidence that hypoglycemia as low as 2.4 mmol/L, lasting more than 60 min, can significantly increase the conduction time of central somatosensory pathways.

Adult↗

Hemodynamic study of intravenous propionyl-L-carnitine in patients with ischemic heart disease and normal left ventricular function.

Propionyl-L-carnitine was given intravenously to ten patients with chronic ischemic heart disease who had normal left ventricular function and had not had a previous myocardial infarction. Subsequently, pulmonary and systemic circulation, left ventricular function, and the relationship between the ventricle and afterload were evaluated. This drug, at a dose of 15 mg/kg, improves ventricular function by easing the load and by enhancing cardiac efficiency. The ejection impedance is reduced with a consequent increase in stroke volume as a result of a) a decrease in systemic and pulmonary resistance and b) an increase in arterial compliance. Arterial pressure is maintained due to an increase in total external heart power. Since the tension time index shows a proportionally smaller increase in the energy requirement, it follows that cardiac efficiency has been improved and ventricle-afterload matching is optimal. These results suggest but do not prove that propionyl-L-carnitine exhibits a positive inotropic property.

Adult↗

Functional and structural abnormalities in patients with dilated cardiomyopathy.

Passive diastolic properties of the left ventricle were determined in 10 control subjects and 12 patients with dilated cardiomyopathy. Simultaneous left ventricular angiography and high fidelity pressure measurements were performed in all patients. Left ventricular chamber stiffness was calculated from left ventricular pressure-volume and myocardial stiffness from left ventricular stress-strain relations with use of a viscoelastic model. Patients with dilated cardiomyopathy were classified into two groups according to the diastolic constant of myocardial stiffness (beta). Group 1 consisted of seven patients with a normal constant of myocardial stiffness less than or equal to 9.6 (normal range 2.2 to 9.6) and group 2 of 5 patients with a beta greater than 9.6. Structural abnormalities (percent interstitial fibrosis, fibrous content) in patients with dilated cardiomyopathy were assessed by morphometry from right ventricular endomyocardial biopsies. Heart rate was similar in the three groups. Left ventricular end-diastolic pressure was significantly greater in patients with cardiomyopathy (18 mm Hg in group 1 and 22 mm Hg in group 2) than in the control patients (10 mm Hg). Left ventricular ejection fraction was significantly lower in groups 1 (37%) and 2 (36%) than in the control patients (66%). Left ventricular muscle mass index was significantly increased in both groups with cardiomyopathy. The constant of chamber stiffness (beta*) was slightly although not significantly greater in groups 1 and 2 (0.58 and 0.58, respectively) than in the control group (0.35). The constant of myocardial stiffness beta was normal in group 1 (7.0; control group 6.9, p = NS) but was significantly increased in group 2 (23.5). Interstitial fibrosis was 19% in group 1 and 43% (p less than 0.001) in group 2 (normal less than or equal to 10%). There was an exponential relation between both diastolic constant of myocardial stiffness (beta) and interstitial fibrosis (IF) (r = 0.95; p less than 0.001) and beta and fibrous content divided by end-diastolic volume index (r = 0.93; p less than 0.001). It is concluded that myocardial stiffness can be normal in patients with dilated cardiomyopathy despite severely depressed systolic function. Structural alterations of the myocardium with increased amounts of fibrous tissues are probably responsible for the observed changes in passive elastic properties of the myocardium in patients with dilated cardiomyopathy. The constant of myocardial stiffness (beta) helps to identify patients with severe structural alterations (group 2), representing possibly a more advanced stage of the disease.

Adult↗

Right ventricular dysplasia: angiographic study.

At the moment, the most reliable method for diagnosing right ventricular dysplasia is considered to be angiography. Morphological alterations such as the presence of akinetic/dyskinetic areas, aneurysmatic dilatations and deep anteroapical fissuring, not necessarily associated with an increase in ventricular volume, are understood to be angiographic criteria indicating dysplasia. To verify their diagnostic value, these abnormalities have been evaluated in: (1) 33 patients suspected of having dysplasia because of PVBs with LBBB morphology and with 'borderline' involvement of the right ventricle or without instrumental evidence of cardiac disease (Group A); (2) 16 subjects with no arrhythmia and normal left ventricular angiography, coronary and bioptic findings (Group B); (3) 36 patients with a clinical, angiographic and bioptic diagnosis of dilated idiopathic cardiomyopathy (Group C). In 48.5% of the patients in Group A, angiography showed localized akinesia/dyskinesia (12 patients), small conical outpouchings persisting during systole (10 patients) and apical deep fissuring (two patients). In 81% of these patients, endomyocardial biopsy showed the presence of fibrous and/or adipose tissue in at least 20% of the examined sample. Angiographic abnormalities suggesting dysplasia were found in none of the normal subjects and only in two of the 36 patients with dilated cardiomyopathy (5.5%).

Adolescent↗

Right ventricular dysplasia: an ultrastructural study.

Ultrastructural observations on myocardial biopsies from patients developing clinical and/or echocardiographic and haemodynamic signs of dysplasia of the right ventricle did not reveal morphological defects of the myocardiocyte contraction apparatus, but showed evidence of fibrosis of the myocardial interstitium and modifications of the structures involved in the transmission of the action potential into the cardiac cells as well as of the junctional system between them. Interstitial adipocytes and intracellular lipid droplets were not increased in number.

Adipose Tissue↗

Increased insulin sensitivity in patients with idiopathic reactive hypoglycemia.

We performed a euglycemic hyperinsulinemic glucose clamp in 20 patients selected from a large number of subjects referred to our clinic with symptoms suggesting reactive hypoglycemia. Diagnosis was made on the basis of blood glucose measurements during symptoms in their daily life and confirmed by a 5-h oral glucose tolerance test. The patients were divided into the following groups: 8 patients with idiopathic reactive hypoglycemia (IRH), i.e. biochemical hypoglycemia associated with symptoms and plasma insulin concentrations in the normal range; 6 patients with nonhypoglycemia (NH), i.e. patients experiencing the symptoms evoking hypoglycemia at essentially normal plasma glucose levels; and 6 patients with alimentary hypoglycemia secondary to previous gastric surgery (GS). Eight normal volunteers formed the control group (N). Hypoglycemia in this study was considered to be present when plasma glucose concentrations were below 2.5 mmol/L. The peak cortisol levels after glycemic nadir were higher (2P less than 0.05) in IRH compared to GS and N. In the same group, a partially deficient glucagon response to hypoglycemia was noted. During the euglycemic clamp, the glucose uptake appeared to be significantly greater in the IRH group than in NH, GS, and N groups (8.13 +/- 0.49 vs. 7.02 +/- 0.35, 6.48 +/- 0.22, and 6.66 +/- 0.42 mg/kg.min, respectively; 2P less than 0.05). Therefore, our data suggest that increased insulin sensitivity represents a feature of idiopathic reactive hypoglycemia.

Adult↗

[Effect of intracoronary and intravenous administration of propranolol on coronary vasomotility at rest and during exercise].

The effect of intracoronary and intravenous propranolol on coronary vasomotion was evaluated in 30 patients with coronary artery disease. Luminal area of a normal and a stenotic coronary segment was determined at rest, during supine bicycle exercise and 5 min after 1.6 mg sublingual nitroglycerin administered at the end of the exercise test using biplane quantitative coronary arteriography. Patients were divided into 3 groups: Group I (n = 12) served as control Group II consisted of 10 patients with intracoronary administration of 1 mg propranolol and Group III of 8 patients with intravenous administration of 0.1 mg/kg propranolol prior to the exercise test. In the control Group there was coronary vasodilation (+23%, p less than 0.01) of the normal and coronary vasoconstriction (-29%, p less than 0.001) of the stenotic vessel segment during bicycle exercise. After sublingual administration of 1.6 mg nitroglycerin there was vasodilation of both normal (+40%, p less than 0.001 vs rest) and stenotic (+12%, NS vs rest) segments. In Group II intracoronary propranolol was not accompanied by a change in coronary area but both normal (+13%, p less than 0.05) and stenotic (+22%, p less than 0.05) segments showed coronary vasodilation during bicycle exercise. After sublingual nitroglycerin there was further vasodilation of both normal (+31%, p less than 0.001 vs rest) and stenotic (+45%, p less than 0.01 vs rest) arteries. In Group III intravenous administration of propranolol was associated with a decrease in coronary luminal area of both normal (-24%, p less than 0.001) and stenotic (-41%, p less than 0.001) segments. During dynamic exercise there was coronary vasodilation of both segments when compared to the data after intravenous injection of propranolol but there was no change in luminal area (normal vessel-2%, NS vs rest; stenotic vessel-3%, NS vs rest) when compared to the resting data. After sublingual administration of 1.6 mg nitroglycerin both normal (+21%, p less than 0.001) and stenotic (+46%, p less than 0.001) segments showed coronary vasodilation. It is concluded that supine bicycle exercise in patients with coronary artery disease is associated with vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Intravenous administration of propranolol is followed by coronary vasoconstriction of both normal and stenotic coronary arteries probably due to secondary mechanisms (reduction in heart rate and contractility) because it is not observed after intracoronary injection of propranolol and it is overridden by bicycle exercise and sublingual nitroglycerin.

Adult↗