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Biomedical subjects

R Riva

Publications and source records attributed to R Riva.

At least 19 recordsLinked to original sources

An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS.

Cervical cord magnetization transfer ratio (MTR) histograms were obtained from 45 patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). The mean values of MTR histogram-derived metrics were not different between CIS patients and healthy control subjects or between patients with and without evidence of disease dissemination in time. Only three patients showed significantly lower cord MTR values than control subjects. These findings suggest the absence of intrinsic structural damage of the cervical cord soon after the onset of CIS suggestive of MS, even in those patients with an early evolution to MS.

Adolescent↗

Neuroradiologic differential diagnosis of cerebral intraparenchymal hemorrhage.

Cerebral intraparenchymal hematoma (IH) is one of the most common causes of sudden onset of focal neurologic deficit. This is particularly true in the acute phase, in which IH appears hyperdense compared to the cerebral tissue. By three to four weeks, it becomes isodense with the cerebral gray matter and hypodense within 2 to 6 months. After contrast media administration, IH shows a peripheral ring of enhancement owing to the breakdown of the blood brain barrier. On magnetic resonance imaging (MRI), the appearance of IH depends upon the paramagnetic effects of the different derivates of hemoglobin and both the magnetic field strength and type of sequences used. In the hyperacute phase, IH appears hyperintense on T2 and hypointense on T1 owing to the presence of oxyhemoglobin. In the acute phase, IH is hypointense on T2 and iso-hypointense on T1 as a consequence of the presence of deoxyhemoglobin, which is converted into methemoglobin by 3 to 5 days. Methemoglobin has a strong paramagnetic effect, so in this phase IH becomes hyperintense on T1 and hypointense on T2. After 2 weeks, methemoglobin is converted in hemosiderin, responsible of the ring of hypointensity surrounding the lesion on T2WI. When an IH has been diagnosed, someone should think about the origin of bleeding. Among the different differential diagnosis, one should think about the possible origin, taking into account some parameters, such as: anamnestic data, site of the lesion, number of lesions, appearance on CT and MRI, and presence of perilesional edema. Computed tomography is a reliable and very fast tool for the diagnosis of IH, but MRI is able to provide additional information about the spontaneous or secondary nature of the hematoma, thus allowing a better characterization of the hemorrhagic lesion.

Brain Edema↗

Mycobacterial testing in hospital laboratories: results from a questionnaire survey in Italy.

Between 1999 and 2001, 355 hospital laboratories in Italy were asked to complete a questionnaire addressing mycobacterial test methods, 1-year workloads and laboratory safety features. Analysis of the data showed that rapid methods for mycobacterial testing were being used by most larger laboratories; however, sub-optimal methods were still in use in small and medium-size laboratories. In a country such as Italy, which has a low prevalence of tuberculosis cases, implementation of rapid technologies, combined with regionalisation of mycobacterial diagnostic services, seems to be the most reasonable and cost-effective strategy.

Bacteriological Techniques↗

Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms.

OBJECTIVES: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. METHODS: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2-40 years). RESULTS: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. CONCLUSIONS: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis.

Abnormalities, Multiple↗

Levodopa pharmacokinetics and dyskinesias: are there sex-related differences?

We examined the potential sex-related differences in levodopa pharmacokinetics and their relation with the presence of dyskinesias in a group of 115 patients (67 men, 49 women) with Parkinson's disease. The patients were given a standard oral dose of levodopa plus benserazide (100/25 mg). The area under the levodopa plasma concentration time curve, corrected for the levodopa test dose (in mg/kg body weight), (AUC(w)) was significantly higher in women than in men, with a reduced oral clearance. No difference in the proportion of men and women experiencing dyskinesias was observed.

Aged↗

Simple and rapid liquid chromatographic-turbo ion spray mass spectrometric determination of topiramate in human plasma.

We present a simple and fast method for the determination of the novel antiepileptic drug topiramate in human plasma by high-performance liquid chromatography coupled with turbo ion spray mass spectrometry. Plasma sample pre-treatment was based on simple deproteinization by acetonitrile. Liquid chromatographic analysis was carried out on a reversed-phase column (C18, 125x4 mm I.D., 5 microm) using acetonitrile-ammonium acetate buffer, pH 6.3 as the mobile phase, at a flow-rate of 0.8 ml/min. Retention time for topiramate was 2.1 min. The detector was a single quadrupole mass spectrometer coupled to a turbo ion spray ion source and a heated nebulizer probe, operating in the positive ion mode. Ion source temperature was off; voltage was +5800 V; nebulizer and curtain gas flow-rates were 6 and 10 ml/min, respectively. Calibration curves for topiramate were linear over the range 1 to 20 microg/ml. Absolute recovery ranged between 92 and 95%. Intra- and inter-assay precision was <4%. The present procedure, omitting extraction and drying steps, is faster and simpler than the previously reported analytical methods for topiramate and was demonstrated to possess adequate sensitivity for routine therapeutic drug monitoring in plasma from patients with epilepsy.

Anticonvulsants↗

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis.

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.

Adult↗

Equine muscular dystrophy with myotonia.

OBJECTIVES: To describe a case of equine muscular dystrophy with myotonia. METHODS: A 5-year-old horse presented with hypertrophy and delayed relaxation of the muscles of the hindlimbs from age 2 months. Testicular atrophy developed from 2 years of age. Action and percussion myotonia was associated with weakness in these muscles, and EMG showed diffuse myotonic discharges and myopathic features. Biopsy of the gluteal muscle showed adipose and connective tissue infiltration, marked variation in muscle fibre size, and moth-eaten, ring and whorled fibres. RESULTS: Injection of apamin, a peptide blocker of calcium-activated potassium channels, which inhibits myotonia in human myotonic dystrophy, was ineffective in blocking myotonic discharges. Discharges promptly abated with 2% lidocaine injection. CONCLUSIONS: Myotonia in this horse is associated with dystrophic changes similar to human myotonic dystrophy, though there are some pharmacological differences.

Anesthetics, Local↗

Validity of hospital discharge diagnoses for the assessment of the prevalence and incidence of amyotrophic lateral sclerosis.

INTRODUCTION: As amyotrophic lateral sclerosis (ALS) is a rare neurological disorder, many sources must be investigated for complete case ascertainment. Hospital discharge diagnoses (HDDs) are a source of administrative data for patients hospitalized for a given disease. The accuracy of HDDs was tested, to assess whether they could be used to trace patients with amyotrophic lateral sclerosis (ALS). METHODS: All the HDDs referring to patients with motor neuron disease (MND) (ICD-9 code 335.2) were identified from primary hospital discharge diagnoses made during the years 1994-95 in six target provinces of the Lombardy region in Northern Italy (total population 2922920). The medical records of the patients were reviewed and each patient was then accepted or rejected according to whether he/she did or did not satisfy the El Escorial criteria for the diagnosis of ALS. The ALS discharge diagnoses filed in the study period in the neurology departments of all the regional hospitals were the 'gold standard'. Newly diagnosed patients registered during the year 1998 in the same provinces served for the calculation of the incidence of the disease. Sensitivity, specificity and positive predictive value were calculated. Data were presented separately for all the patients and those who were indicated as first hospital admissions. RESULTS: During the study period a total of 1012122 hospital discharge records were coded in the six index provinces. The ICD-9 code 335.2 was reported in 408 of these (0.04%). These discharge diagnoses were made in 267 patients, 245 of whom were resident in Lombardy at the time of hospital admission. The hospital records of 237 cases were examined. In 95 of these the medical records showed a diagnosis other than ALS. Other motor neuron diseases were listed for 50 patients. Thirteen additional cases were traced through neurology department files. The sensitivity of the HDDs was 91.6%, the specificity 99.9%, the positive predictive value 65.4%. The corresponding values for first-hospitalized patients were 97.7, 99.9, and 37.3. The overall ALS incidence rate obtained from the HDDs was 2.1 per 100000 (95% CI 1.3-3.3). he corresponding rate calculated after exclusion of the false positives and inclusion of the false negatives was 0.8 (95% CI 0.1-2.1) and that obtained using the 1998 cases registered in the same areas was 1.6 (95% CI 0.7-2.7). CONCLUSIONS: The incidence of ALS is overestimated when HDDs are used for the estimate. Nevertheless, with improved quality, administrative data could be useful for the estimate of prevalence and incidence.

Admitting Department, Hospital↗

Levodopa therapy monitoring in patients with Parkinson disease: a kinetic-dynamic approach.

The authors assessed differences in both therapeutic and dyskinesia-matched concentrations of levodopa by kinetic-dynamic modeling in a large cohort of patients with Parkinson disease grouped by severity of symptoms. The goal was to provide a kinetic-dynamic approach to levodopa therapy monitoring to assist treating physicians in rationalizing patients' drug schedules in line with disease progression. Eighty-six patients, grouped according to Hoehn & Yahr (H&Y) clinical stage (H&Y I, n = 23; II, n = 25; III; n = 25; IV, n = 13) enrolled in the study. After a 12-hour levodopa washout each patient was examined using a standard oral levodopa test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects, and dyskinesia ratings. The kinetic-dynamic modeling for both effects was carried out according to the "link" effect compartment model and sigmoidal pharmacodynamic model. Levodopa plasma kinetics did not differ among patient groups. Duration of motor response was significantly (p < 0.001) curtailed in patients in advanced clinical stages whereas dyskinesia duration showed minor changes among the three affected groups (H&Y II, III, and IV). Median effective concentrations (EC 50 ) were increased at the more advanced clinical stage (p < 0.001), from a median 0.2 microg/mL in patients at H&Y stage I to 0.9 microg/mL in patients at H&Y stage IV, whereas the maximum effect showed less consistent changes among the four groups. Intrasubject levodopa therapeutic concentrations were lower than values for dyskinesias in patients at the moderate stage of the disease, equaling dyskinesia-matched drug concentrations in the more affected patients. These findings are in line with previous observations of major changes in levodopa concentration-effects relationship with disease progression and support a stratification of patients with Parkinson disease according to kinetic-dynamic modeling. From a practical point of view, knowledge of individual patients' kinetic-dynamic variables can help the physician assess patients' clinical needs objectively and optimize levodopa dosing according to disease progression.

Adult↗

Efficacy of lamotrigine add-on therapy in severe partial epilepsy in adults with drop seizures and secondary bilateral synchrony on EEG.

OBJECTIVES: To evaluate the efficacy of lamotrigine (LTG) add-on therapy in drug-resistant, partial epilepsy with epileptic drop attacks (EDA) and secondary bilateral synchrony (SBS) on EEG. METHODS: We carried out a single-center, open-label, prospective study on a restricted group of patients experiencing an EDA frequency of at least one/month during the previous year regardless of multiple antiepileptic drug (AED) trials. Study design consisted of three phases: a 3-month baseline period, a 4-month period in which LTG was titrated and a 9-month maintenance dose observational period. LTG add-on therapy depended on valproate (VPA) association, with a maximum of 200 mg/day with VPA and 600 mg/day in the absence of VPA. Every three months, patients underwent clinical, hematological and EEG evaluation including plasma level of AEDs. To assess the efficacy of LTG add-on therapy, patients were required to keep a detailed seizure diary throughout the study. RESULTS: Fourteen patients (nine men and five women), aged from 21 to 51, were included in the study. All of them had complex partial seizures (CPS), besides EDA, and half of them had secondarily generalized seizures (SGS). Two of the 14 patients had to stop LTG due to side effects, although one of them was seizure-free after LTG. Twelve patients completed the study. The improvement was more than 50% for every type of seizure. SGS disappeared in three cases and improved by more than 50% in another three cases. EDA disappeared in six patients; and improved with more than 50% EDA reduction in five patients. CPS disappeared in two patients and improved by more than 50% in eight. EEG improved in nine cases, with SBS disappearing in six patients. CONCLUSIONS: We have demonstrated a good efficacy of LTG adjunctive therapy on EDA. Results include control of SGS and improvement of EEG tracing.

Adult↗

A randomized controlled trial of recombinant interferon beta-1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group.

OBJECTIVE: To evaluate the efficacy of recombinant interferon beta (IFNbeta)-1a in the treatment of ALS. BACKGROUND: It has been proposed that IFNs affect the progression of ALS by interfering with putative immune mechanisms involved in the pathogenesis of the disease. METHODS: Patients (n = 61) 40 to 70 years of age with a 6- to 24-month history of confirmed ALS with mild to moderate disability received IFNbeta-1a, 12 mIU (n = 31), or placebo (n = 30) subcutaneously three times a week for 6 months and were followed up for an additional 6 months. Patients were assessed after 4, 12, 24, 36, and 48 weeks. Medical Research Council scale, Norris scale, and bulbar scores as well as forced vital capacity were used to assess disability. Selected electrophysiologic measures (latency, amplitude, and duration of the compound muscle action potential) were also used. RESULTS: Twenty patients randomized to IFNbeta-1a and 17 patients given placebo completed the study. A total of 16 patients receiving IFNbeta-1a became non-self-supporting compared with 16 on placebo (52% versus 53%). There were no significant differences between the two treatment groups for any of the measures of disease progression and disability. Deaths were reported in six patients treated with IFNbeta-1a and four patients on placebo. Adverse events were reported more frequently with IFNbeta-1a (77% of patients) compared with placebo (57%), with flu-like symptoms and local erythema being the commonest complaints. CONCLUSIONS: This pilot study suggests that IFNbeta-1a is not effective in the treatment of ALS.

Aged↗

Reduced platelet glutamate uptake in Parkinson's disease.

Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34PD patients and 21 age-related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = -0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD.

Analysis of Variance↗

Effect of felbamate on clobazam and its metabolite kinetics in patients with epilepsy.

The authors report preliminary findings on the effect of the new generation antiepileptic drug (AED) felbamate (FBM) on steady state plasma concentrations of clobazam (CLB), a benzodiazepine (frequently used as add-on therapy in patients with refractory epilepsy) and its active metabolite n-desmethyl-clobazam (N-CLB). The authors prospectively collected plasma samples from 66 children and adults with epilepsy receiving chronic CLB therapy. On the basis of concomitant AEDs, patients were divided into three subgroups otherwise comparable for age and weight-adjusted daily dose of CLB: group A (n = 22), receiving CLB monotherapy or CLB plus AEDs without inducing properties of cytochrome P450 (CYP) metabolism, namely valproic acid (VPA) or lamotrigine (LTG); group B (n = 28), receiving CLB plus AED inducer polytherapy (carbamazepine, phenobarbital, phenytoin), even associated with VPA (n = 9) or LTG (n = 12); group C (n = 16), receiving CLB plus FBM, associated with AED inducers, VPA or LTG. Level to weight-adjusted dose ratio (L/D) of CLB in groups B and C was twofold lower compared to group A (p < 0.001). L/D of N-CLB was twofold higher in group B and fivefold in group C compared to group A (p < 0.00 1). The metabolite-to-parent drug ratio shifted from a median value of 2.8 in group A to 13 in group B, and up to 29 in patients receiving polytherapy with FBM (p < 0.001). These data confirm previous reports of a significant increase in CLB clearance in patients receiving AED inducers, leading to an accumulation of its main metabolite. They also provide novel evidence of a further marked increase in N-CLB plasma concentrations in patients receiving FBM cotherapy. From a clinical point of view, this finding should be kept in mind in explaining possible toxicity in patients on complex AED polytherapy. Furthermore, knowledge of the in vivo interaction between CLB and FBM could help in identifying the CYP isoforms involved in the metabolism of both CLB and N-CLB.

Adolescent↗

Effect of meal timing on the kinetic-dynamic profile of levodopa/carbidopa controlled release [corrected] in parkinsonian patients.

OBJECTIVE: The aim of the study was to assess the effect of the time of ingestion of a meal on the pharmacokinetics and pharmacodynamics of a levodopa/carbidopa controlled-release formulation in parkinsonian patients on chronic levodopa therapy. METHODS: The kinetic-dynamic profile of one tablet of controlled-release levodopa/carbidopa 200/50 mg was monitored in eight patients, according to an intrasubject randomized cross-over design in two different sessions. A standard meal was consumed by the patients after they had fasted for 15-17 h, on one occasion 30 min before the ingestion of the test dose, and on the other occasion 2 h after the ingestion of the same drug dose. Blood venous samples for analysis of plasma levodopa and its metabolite 3-O-methyldopa were drawn at 20-min intervals up to 6 h after dosing. Motor response to the levodopa test dose was assessed by the finger tapping and walking speed tests at the same times as blood was drawn. RESULTS: Controlled release [corrected] levodopa intake after meals resulted in a significant delay in drug absorption, with an almost twofold increase in time of initial appearance of levodopa in plasma and time to peak plasma concentration. Peak plasma drug concentrations were not significantly different in the two experimental conditions; the area under the 6-h plasma concentration-time curve showed an average reduction of 24% in the fed condition, partly reflecting the incomplete assessment of levodopa absorption, within the 6 h of examination, due to 5-h delayed peak plasma levodopa concentration in two patients. With reference to levodopa pharmacodynamics, time to onset of motor response was significantly delayed and duration of motor response significantly curtailed in the fed condition, while the magnitude and overall extent of motor effect were unchanged. CONCLUSIONS: In keeping with previous findings on levodopa standard-release preparations, these data show that time of meal ingestion is an important determinant of levodopa disposition, even from controlled-release preparations in parkinsonian patients. From a clinical point of view, these results help to explain some of the delayed, curtailed and even lacking responses that often complicate afternoon motor performances in patients at the more advanced stages of the disease.

Aged↗