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Biomedical subjects

P Cortelli

Publications and source records attributed to P Cortelli.

At least 73 records · Page 4Linked to original sources
PubMed1998

A levodopa kinetic-dynamic study of the rate of progression in Parkinson's disease.

OBJECTIVE: The aims of the study were to follow prospectively the intrasubject progression of idiopathic PD in a cohort of patients using levodopa kinetic-dynamic modeling and to assess the relation between the rate of progression of the disease and patients' different clinical characteristics. METHODS: Thirty-four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow-up. Each patient was examined at 1-year intervals over a median 4 years by a standardized oral levodopa test. The primary measure outcome was the computed half-life of levodopa in the "effect compartment" (t1/2eq), a proposed indicator of nigrostriatal dopaminergic functionality and integrity. RESULTS: Values of levodopa t1/2eq correlated negatively with severity of symptoms (r = -0.652, p < 0.0001) and decreased over the years together with a worsening of patients' clinical stage (p < 0.001). The rate of reduction in drug t1/2eq was more rapid in patients at the earlier stages of the disease compared with the more advanced ones, falling from a median annual reduction of 37 minutes in patients at initial Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p < 0.001). Patients without tremor at onset, otherwise comparable to patients with tremor for baseline values of levodopa t1/2eq, disease severity, duration, and daily dose of levodopa, tended to show a higher rate of reduction in levodopa t1/2eq than patients with tremor. Overall, patients' annual reduction in levodopa t1/2eq over baseline values averaged 17+/-9%. CONCLUSIONS: These results are in keeping with PET findings on the objective assessment of idiopathic parkinsonism evolution, and they support the suggestion that levodopa pharmacodynamic modeling may offer a practical clinical tool to assess indirectly the functional integrity of the nigrostriatal dopaminergic system over time in parkinsonian patients.

Adult↗
PubMed1998

Fatal familial insomnia in a new Italian kindred.

The authors report a new kindred with fatal familial insomnia (FFI)--an inherited prion disease. The propositus had behavioral, sleep, cognitive, and motor impairment associated with thalamic and olivary atrophy. Spongiosis was confined to the parahippocampal gyrus. Protease-resistant prion protein (PrP(res)) was present with widespread distribution. The propositus fits the histopathology of FFI with similar clinical duration and confirms the role of disease duration in determining histopathology and PrP(res) distribution in FFI.

Age of Onset↗
PubMed1997

Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study in vivo brain and muscle bioenergetics in a male patient with Leber's hereditary optic neuropathy (LHON) and mtDNA mutation at 11,778 bp who developed spastic paraparesis with white matter lesions on brain MR imaging. The study was performed before and during treatment with idebenone (135 mg t.i.d.) and after withdrawal. Clinical amelioration and worsening were associated with parallel changes in brain and skeletal muscle bioenergetics following the administration or withdrawal of idebenone. Reversal of paraparesis by idebenone was paralleled by normalization of 31P-MRS, serum lactate and central motor conduction. Extra-ocular neurological dysfunction in LHON may be amenable to treatment by appropriate quinones.

Adult↗
PubMed1997

Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache.

Phosphorus MR spectroscopy (31P-MRS) was used to quantify skeletal muscle bioenergetics and proton efflux in 63 patients with migraine (23 with migraine without aura, MwoA, 22 with migraine with aura, MwA, and 18 with prolonged aura or stroke, CM) and in 14 patients with cluster headache (CH), all in an attack-free period. At rest mitochondrial function was abnormal only in CM, as shown by a low phosphocreatine (PCr) concentration. At the end of a mixed glycolytic/aerobic exercise all three migraine groups showed a significantly smaller decrease of cytosolic pH compared to controls with a similar end-exercise PCr breakdown, while end-exercise pH was normal in cluster headache patients. The normal rate of proton efflux in all headache groups suggests that the reduced end-exercise acidification was due to a reduction of glycolytic flux in migraine patients. The maximum rate of mitochondrial ATP production (Qmax), calculated from the rate of post-exercise PCr recovery and the end-exercise [ADP], was low in cluster headache patients as well as in migraine patients except MwoA. In migraine the degree of the mitochondrial impairment, that apparently is associated with a reduced glycolytic flux, is related to the severity of the clinical phenotype.

Adolescent↗
PubMed1997

Searching for migraine genes: exclusion of 290 cM out of the whole human genome.

A linkage and association analysis was made on 14 Italian families with recurrent migraine. We analyzed five chromosomal regions surrounding the candidate genes 5HT1D (1p36.3-34.3), 5HT1B (6q13), 5HT2A (13q14-21), 5HT transporter (17q11.2-12), CACNLB1 (17q11.2-22) and FHM (19p13), using 29 DNA polymorphic markers. All two-point lod scores were negative, and the chi 2 sib-pair analyses were not significant, thus indicating the probable exclusion of these regions as sites of migraine genes in our population.

Chromosome Mapping↗
PubMed1997

Power spectral analysis of heart rate and diastolic blood pressure variability in migraine with and without aura.

Autonomic function in migraineurs during headache-free periods was studied by means of cardiovascular reflexes and power spectral analysis of heart rate and diastolic blood pressure variability. We examined 56 patients: 37 suffering from migraine without aura and 19 from migraine with aura. Cardiovascular responses to the tilt test and Valsalva manoeuvre showed a normal function of the overall baroreceptor reflex arc. Normal heart rate responses to Valsalva manoeuvre and deep breathing suggested an intact parasympathetic function. Power spectral analysis of both heart rate and diastolic blood pressure variability in basal conditions and during orthostatic test showed similar sympathovagal interactions modulating cardiovascular control in migraine patients and in controls.

Adult↗
PubMed1997

Motor overactivity and loss of motor circadian rhythm in fatal familial insomnia: an actigraphic study.

The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.

Body Mass Index↗
PubMed1997

Undiagnosed sleep-disordered breathing among male nondippers with essential hypertension.

OBJECTIVE: A blunting of the nocturnal fall in arterial blood pressure is found in a minority of patients (nondippers) with essential hypertension. We tested whether sleep-disordered breathing (snoring and apnea or hypopnea) might explain such a finding for male patients, among whom its prevalence is much higher. SETTING AND PATIENTS: We studied 100 new cases of hypertension in men, observed consecutively by a local group of general practitioners and diagnosed essential hypertensives in a referral clinic. By using 24 h ambulatory blood pressure monitoring with a SpaceLabs 90207 device, 15 patients were classified initially nondippers (daytime ambulatory blood pressure > or = 136/87 mmHg; night-time decrease by < 10% of the daytime mean), but only 11 were confirmed to be nondippers by continuous blood pressure monitoring with a Finapres device. Ten dippers matched by age, body mass index and mean 24 h blood pressure were used as controls. MAIN OUTCOME MEASURES: Parameters of nocturnal polysomnography. RESULTS: During polysomnography, the nondippers exhibited a blunting of the sleep-related fall in blood pressure and an increased variability in blood pressure associated with sleep-disordered breathing (heavy snoring for all, with an apnea or hypopnea index > 10 in 10 cases). Six of the control patients breathed normally and four snored nonapneically. There was a normal fall in nocturnal blood pressure in all 10 cases. CONCLUSIONS: The nondipper condition appears to be associated with undiagnosed apneic snoring for an unselected population of previously untreated male subjects with a diagnosis of essential hypertension. Ambulatory blood pressure monitoring of such patients is of limited diagnostic value.

Adult↗
PubMed1997

Deficit of brain and skeletal muscle bioenergetics and low brain magnesium in juvenile migraine: an in vivo 31P magnetic resonance spectroscopy interictal study.

We used phosphorus magnetic resonance spectroscopy (31P MRS) to investigate in vivo the brain and skeletal muscle energy metabolism of 15 children with migraine with aura in interictal periods. Brain 31P MRS disclosed low phosphocreatine and high inorganic phosphate contents, and high intracellular pH in all patients. Calculated [ADP] and the relative rate of mitochondrial oxidation were higher in the brain of patients than in control subjects, whereas the phosphorylation potential was lower. Brain intracellular free Mg2+ concentration was reduced by 25% in patients. Abnormal skeletal muscle mitochondrial respiration was also disclosed in 7 of 15 patients as shown by the slow rate of phosphocreatine postexercise recovery. The multisystem bioenergetic failure found in patients with juvenile migraine is comparable to that found in adults with different types of migraine.

Adolescent↗
PubMed1997

Phosphorus magnetic resonance spectroscopy in cluster headache.

We performed in vivo MR spectroscopy phosphorus (31P-MRS) on the brain and skeletal muscles of 14 patients affected with cluster headache (CH). We examined patients in interictal periods, and also examined nine of them during the cluster period, although not during the attack. Brain 31P-MRS showed reduced phosphocreatine (PCr) levels, an increased ADP concentration (calculated from the creatine kinase equilibrium), a reduced phosphorylation potential, and a high relative rate of ATP biosynthesis (V/Vmax %). The inorganic phosphate (P(i)) content was increased during the cluster period. Ten of 13 patients also showed a slow rate of PCr recovery in muscle after the exercise. 31P-MRS in CH patients showed abnormalities of brain and skeletal muscle energy metabolism comparable with those seen in various types of migraine, thus leading us to suggest a similarity in biochemical pathogenic mechanisms between CH and migraine.

Adenosine Diphosphate↗
PubMed1997

REM sleep behavior disorders in multiple system atrophy.

We report the results of clinical and polysomnographic investigations on 39 consecutive multiple system atrophy (MSA) patients. Twenty-seven patients (69%) reported nocturnal motor paroxysmal episodes related to dreams, suggesting the clinical diagnosis of REM sleep behavior disorder (RBD). In 12 of them (44%), RBD preceded the clinical onset of the disease by more than 1 year. In seven (26%), the RBD onset was concomitant with and in eight (30%) was at least 2 years after the appearance of motor or autonomic symptoms. On polysomnographic recordings, 35 of 39 MSA patients (90%) had RBD. Other polysomnographic findings included nonclinical obstructive sleep apnea in 6 patients, laryngeal stridor in 8 patients, and periodic limb movements during sleep in 10 patients. Our data show that RBD represents the most common clinical sleep manifestation and polysomnographic finding in patients with MSA. RBD can frequently herald the appearance of other MSA symptoms by years. Extended polysomnographic montages are recommended in MSA sleep studies.

Adult↗
PubMed1997

Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1 mutations and correlation with the mitochondrial genotype.

To clarify the bioenergetic relevance of mtDNA mutations in Leber's hereditary optic neuropathy (LHON), we investigated affected individuals and healthy carriers from six Italian LHON families harboring the 11778/ND4 and the 3460/ND1 mtDNA mutations. The enzymatic activities of mitochondrial complex I and its sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied in mitochondrial particles from platelets, in correlation with mtDNA analysis of platelets and leukocytes. In platelets homoplasmic for mutant mtDNA, both 11778/ND4 and 3460/ND1 mutations induced resistance to rotenone and the 3460/ND1 mutation also provoked a marked decrease in the specific activity of complex I. Individuals heteroplasmic in platelets for either mutation showed normal biochemical features, indicating functional complementation of wild-type mtDNA. There was no correlation between the clinical status and mtDNA homo/heteroplasmy in platelets, but the biochemical features correlated with the mitochondrial genotype of platelets. In some cases, the degree of mtDNA heteroplasmy differed in platelets and leukocytes from the same individual with a prevalence of wild-type mtDNA in the platelets. These results imply that biochemical studies on mitochondrial diseases should always be integrated with mtDNA analysis of the same tissue investigated and also suggest that the mtDNA analysis on the leukocyte fraction, as usually performed in LHON, does not necessarily reflect the mutant genotype level of other tissues. The differential tissue heteroplasmy may be more relevant than previously thought in determining disease penetrance.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein.

We used [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and PET to study regional cerebral glucose utilization in seven patients with fatal familial insomnia (FFI), an inherited prion disease with a mutation at codon 178 of the prion protein gene. Four patients were methionine/methionine homozygotes at codon 129 (symptom duration, 8.5 +/- 1 months) and three were methionine/valine (MET/VAL129) heterozygotes (symptom duration, 35 +/- 11 months). A severely reduced glucose utilization of the thalamus and a mild hypometabolism of the cingulate cortex were found in all FFI patients. In six subjects the brain hypometabolism also affected the basal and lateral frontal cortex, the caudate nucleus, and the middle and inferior temporal cortex. Comparison between homozygous or heterozygous patients at codon 129 showed that the hypometabolism was more widespread in the MET/VAL129 group, which had a significantly longer symptom duration at the time of [18F] FDG PET study. Comparison between neuropathologic and [18F] FDG PET findings in six patients showed that areas with neuronal loss were also hypometabolic. However, cerebral hypometabolism was more widespread than the histopathologic changes and significantly correlated with the presence of protease-resistant prion protein (PrPres). Our findings indicate that hypometabolism of the thalamus and cingulate cortex is the hallmark of FFI, while the involvement of other brain regions depends on the duration of symptoms and some unknown factors specific to each patient. The present data also support the notion that PrPres formation is the cause of neuronal dysfunction in prion diseases.

Adult↗
PubMed1997

A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings.

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.

Adolescent↗
PubMed1997

A multinational investigation of the impact of subcutaneous sumatriptan. II: Health-related quality of life.

The aim of this prospective sequential multinational (5 countries) study was to concurrently evaluate the effects of subcutaneous sumatriptan on clinical parameters, health-related quality-of-life (HRQOL) measures, workplace productivity and patient satisfaction. This report presents the HRQOL results. 582 patients (aged 18 to 65 years) with moderate to severe migraine received their customary antimigraine therapy for 12 weeks and then subcutaneous sumatriptan for 24 weeks. The Short Form-36 Health Survey and the Migraine-Specific Quality of Life Questionnaire were completed at a screening visit (base-line), at the end of the 12-week customary therapy phase, and at 12 and 24 weeks of the sumatriptan phase. Scores for most of the Short Form-36 dimensions improved significantly (p < 0.05) after 12 and 24 weeks of sumatriptan therapy compared with 12 weeks of customary therapy, in each country. Similarly, scores on all Migraine-Specific Quality of Life Questionnaire dimensions were significantly (p < 0.05; paired t-test) improved after 12 weeks (in all countries) and 24 weeks (in 4 of 5 countries) of sumatriptan therapy compared with 12 weeks of customary therapy. This study demonstrates that, in 5 countries, treatment of migraine attacks with subcutaneous sumatriptan compared with customary therapy was associated with improvements in HRQOL, as measured by both general health status and disease-specific instruments.

Adolescent↗
PubMed1997

A multinational investigation of the impact of subcutaneous sumatriptan. III: Workplace productivity and non-workplace activity.

This report presents the workplace productivity and non-workplace activity results of a multinational study of the effects of subcutaneous sumatriptan 6 mg in the acute treatment of migraine compared with patient's customary therapy. Patients diagnosed with migraine treated their symptoms for 24 weeks with subcutaneous sumatriptan after a 12-week period of treating symptoms with their customary (non-sumatriptan) therapy. Patients used diary cards to record information concerning the effects of migraine on workplace productivity and non-workplace activity time. The average workplace productivity time lost was 23.4 hours per patient during 12 weeks of customary therapy, compared with 7.2 and 5.8 hours per patient during the first and second 12-week periods of sumatriptan therapy, respectively. An average of 9.3 hours of non-workplace activity time was lost per patient during the customary therapy phase, compared with 3.2 and 2.8 hours during the first and second 12-week periods of sumatriptan therapy, respectively. Treatment of migraine with subcutaneous sumatriptan compared with customary therapy was associated with an average gain per patient of approximately 16 hours of workplace productivity time and 6 hours of non-workplace activity time, over a 3-month period.

Adolescent↗
PubMed1997

A multinational investigation of the impact of subcutaneous sumatriptan. IV: Patient satisfaction.

This report describes the patient satisfaction results from a prospective, sequential, multinational study. The study was conducted to concurrently evaluate the effects of sumatriptan, compared with customary therapy, on clinical parameters, health-related quality of life, productivity and patient satisfaction in adult patients with moderate to severe migraine. Patients treated migraine attacks for 12 weeks with their customary therapy, followed by 24 weeks' treatment with subcutaneous sumatriptan 6 mg. A questionnaire was conducted at the end of each study phase, or retrospectively at the end of the study, to assess patient satisfaction with customary therapy and sumatriptan. Sumatriptan was considered by most patients (67 to 85%) to be dependable and fast-acting, and to have a long duration of effect, allowing a quick return to normal activities. By comparison, 15 to 32% of patients considered that their customary therapy possessed the same attributes. However, customary therapy was considered to be easy/very easy to use by 82% of patients compared with 62% for subcutaneous sumatriptan. 89% of patients indicated that they would use sumatriptan again in the future. This study demonstrates that treatment of migraine attacks with subcutaneous sumatriptan for 24 weeks is associated with greater patient satisfaction as regards specific drug attributes than customary therapy.

Adolescent↗