Neurologists and patients' associations: alliances and conflicts.
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Biomedical subjects
Publications and source records attributed to M Gasparini.
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Patients with left unilateral neglect bisect long horizontal lines to the right of the true centre. However, when given short lines, many of the same patients mark the midpoint to the left of the true centre, towards the otherwise neglected space. This paradoxical phenomenon has been termed 'cross-over' and is difficult to explain based on current accounts of the neglect syndrome. To explore the causes of cross-over, in a first study we evaluated bisection of 20, 100 and 200 mm horizontal lines in groups of unilateral brain-damaged patients with neglect and hemianopia, with neglect and no hemianopia, with hemianopia and no neglect and without neglect or hemianopia. Cross-over of 20 mm lines was found only in neglect patients with hemianopia. To ascertain further the influence of visual field defects on cross-over, in a second study we compared the performance of two right-brain-damaged patients with contralesional neglect and inferior quadrantanopia with that of a patient with inferior quadrantanopia and no neglect. Patients bisected lines oriented so as to cross or uncross the blind quadrant of the visual field. When short 20 mm lines crossed the blind quadrant, neglect patients showed cross-over; when the same lines crossed the seeing quadrants cross-over was absent. These findings were confirmed by the examination of a neglect patient with sparing of the central 5 degrees of the contralesional left visual hemifield in the right eye and no sparing in the left eye. In monocular viewing, cross-over was present when 20 mm lines were bisected with the left eye and absent when bisected with the right eye. Recording of eye movements showed that at the moment of bisection left eye fixations shifted towards the contralesional line endpoint whereas right eye fixations remained anchored to the centre of the line. With long lines, both eyes deviated ipsilesionally. These results show that in neglect patients ipsilesional deviation in the bisection of long lines turns into apparently paradoxical contralesional bisection of short ones only when these cross a retinotopically blind sector of the neglected space. Cross-over seems to depend on the small spatial effects produced by reflexive contralesional gaze shifts allowing eccentric fixations with the seeing hemifield. During the bisection of long lines, these effects are cancelled out by the strong attentional deviation induced by the marked extension of the ipsilesional line segment. This explanation establishes coherence between cross-over and current accounts of the neglect syndrome.
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A new, rapid and sensitive method is reported for the multiresidual determination of type A (diacetoxyscirpenol, HT-2 toxin, T-2 toxin) and type B (nivalenol, deoxynivalenol, fusarenon X, 15-O-acetyl-4-deoxynivalenol) trichothecenes in wheat flour samples. Sample extraction was performed with acetonitrile/water mixtures. Mycosep columns were used for a fast and effective clean-up procedure. The analytes were separated by HPLC with a RP C18 column by means of a gradient elution and detected in an ESI-interfaced single quadrupole mass spectrometer. Type B and type A trichothecenes were monitored in the negative and in the positive ion mode, respectively. The method performance is reported in terms of linearity (r2 = 0.999), specificity, accuracy (recoveries from 70-120%) and precision (CV% = 5), the LOQs are in the range 10-20 microg/Kg.
A method for the simultaneous LC-fluorescence detection (FLD) determination of eight trichothecenes A and B by pre-column derivatization with coumarin-3-carbonyl chloride, a highly fluorescent fluorophore, has been developed. The reaction conditions (temperature, reaction time, reactant ratios) were optimized to give a reproducible quantitative conversion. All derivatives were characterized by LC-MS. The chromatographic parameters were optimized (column, eluent) to give a very good separation of three type A (diacetoxyscirpenol, T-2 toxin, HT-2 toxin) and five type B trichothecenes [deoxynivalenol (DON), nivalenol, fusarenon-X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol]. The best conditions were obtained on a narrow-bore C18 column with a water-methanol gradient. The detection limits (S/N = 3:1) in grain samples, with an injected volume of 5 microl, were 0.2-1 ng/g for all trichothecenes. These values are more than one order of magnitude lower than those of other LC-FLD and LC-MS methods and are similar to those obtained by GC-MS. The calibration curves were linear between 100 and 2500 ng/g. The method was successfully applied to the analysis of a certified wheat reference material, after solvent extraction and clean-up on a Mycosep column, obtaining a good recovery (89% for DON) and a high accuracy (z-score value: 0.67).
OBJECTIVE: To assess patients who have had a stroke for the subsequent development of poststroke dementia (PSD) and to determine if the characteristics of delayed PSD (dPSD) vary in the long-term follow-up. METHODS: Nondemented patients were followed from 6 months after stroke onset for 4 years. Dementia was diagnosed by International Classification of Diseases-10 criteria; dementia etiology was diagnosed by the National Institute of Neurological and Communication Disorders and Stroke/Alzheimer's Disease and Related Disorders Association and National Institute of Neurologic Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria. Neuroimaging and neuropsychological tests were repeated annually. RESULTS: During a 2-year period, 191 stroke patients were enrolled. By the end of the follow-up period, 41 (21.5%) patients had developed dementia. At the Cox regression analysis, dPSD was associated with cortical atrophy (hazard ratio [HR] = 3.4, 95% CI 1.5 to 7.9), age (HR = 3.3, 95% CI 1.4 to 7.8), and multiple ischemic lesions (HR = 2.5, 95% CI 1.2 to 4.8). The Kaplan-Meier analysis showed a significant difference between the incidence of dPSD subtypes (log-rank test; p = 0.002). CONCLUSIONS: During the 4-year follow-up, the incidence of dementia increased gradually, shifting from an Alzheimer disease-type picture in the first years to a vascular dementia type later in years 2 to 4.
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The analysis of expression signatures is a powerful tool for the classification of cancer and other tissue samples. Several protocols and platforms are available on the market, and these lead to both confirmatory and complementary results. We review the main processing techniques for cross-platform comparisons and the different tissue sources for cancer profiling. Some examples and the cross-interpretation of bibliographic data related to prostate cancer are also presented.
One of the many commercial technologies for genotyping single nucleotide polymorphisms (SNPs) is template direct dye-terminator incorporation with fluorescence-polarization (TDI-FP assay). It is a single-base extension assay followed by reading the fluorescence polarization values in an appropriate instrument. We have evaluated the suitability of the TDI-FP technique to detect haploid uniparentally inherited DNA polymorphisms on the nonrecombining portion of the Y chromosome. A sample of 47 individuals has been genotyped for 8 Y chromosome biallelic markers. The SNP typing was blindly duplicated by the denaturing high-performance liquid chromatography (DHPLC) technique for comparison. In the cases under examination the TDI-FP assay was able to resolve an allelic state fully. Such a result showed 100% concordance indicating how efficiently the TDI assay can be used to genotype Y chromosome DNA SNPs. However, a percentage of indeterminate genotypes remained unresolved by simple visual inspection: it varied from 0% to 11% depending on the SNP locus and on the success of amplification. This is consistent with previous findings. A maximum likelihood classificatory analysis allowed some of the indeterminate genotypes to be assigned and some potentially misclassified samples to be identified. Their percentage remains relatively high despite retyping and therefore alternative techniques for these noncompliant situations are required.
The classic old definition of congenital heart block by Yater (1929) is still generally accepted: 'Heart block established in a young patient. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis'. However, other definitions are used. We systematically reviewed 1825 cases from 38 separate studies. We conclude that complete AV blocks detected in utero in the absence of structural abnormalities differ from blocks detected later in life with respect to pathogenesis (they are generally associated with maternal anti-Ro/SSA antibodies), poorer childhood prognosis, increased risk of developing late-onset dilated cardiomyopathy, different maternal clinical features and increased risk of recurrence in future pregnancies. For these reasons we propose a new modern definition of congenital complete AV block which might be acceptable to cardiologists, rheumatologists, pediatricians and obstetricians: 'an AV block is defined as congenital if it is diagnosed in utero, at birth or within the neonatal period (0-27 days after birth)'.
Aretrospective hospital-based case-control study was performed with the aim to evaluate the association between exposure to anesthesia and Alzheimer's disease (AD). A total of 115 AD patients, 230 Parkinson's disease (PD) patients and 230 patients with non-degenerative neurological disease were studied. Each AD case was matched for sex, age (+/-3 years) and geographic area of residence with four controls (2 PD patients and 2 with other neurological disease). Information about exposure to general anesthesia and other variables was gathered through hospital records. No associations were found between the risk of AD and the exposure to anesthesia in the 1 and 5 years preceding disease onset, nor between the risk of AD and the number of surgical operations. A significant difference was observed between the mean age of AD patients and controls undergoing surgical procedures. The present study reveals a lack of association between exposure to general anesthesia and AD. Prospective epidemiological studies are needed in order to investigate levels of exposure to anesthesia, as well as any possible relationships between anesthetic exposure and genetic factors (e. g. APOEepsilon4 genotype).
In the last two years, the environmental theory on the aetiology of Parkinson disease has acquired new data. From an experimental point of view, a new model of parkinsonism induced by rotenone, a diffuse insecticide, has been proposed, and in vitro studies have provided proof that several pesticides stimulate the formation of alpha-synuclein fibrils (one of the principal constituents of Lewy bodies). Moreover, a meta-analysis of all case-control studies so far performed showed a positive, statistically significant association between pesticide exposure and PD. In this context, we are performing a cohort study on 5575 licensed pesticide users in the province of Viterbo. After 27 years of follow-up, 4788 subjects are still alive. The aim of this study is to measure the prevalence of Parkinson's disease in a large group of workers with theoretically increased risk.
AIMS: Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. METHODS AND RESULTS: In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16+/-4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P=0.02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations (P=0.05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. CONCLUSION: Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing.
27 patients with essential tremor (ET) were studied to determine the cognitive feature of this condition. 15 familial cases and 12 cases with a family history Parkinson's disease (PD) were identified. Performances on frontal lobe tasks of ET patients were compared with those of 15 patients with PD and 15 healthy control subjects. The ET patients showed significant impairments both in attentional and conceptual thinking tasks, similar to those observed in the PD group. Despite the nosographic independence of the two conditions, data showed that the frontal lobe feature of ET was similar to those of PD, thus possibly suggesting a common dysregulation of dopamine pathways.
OBJECTIVES: To evaluate the effect of 3 month therapy with donepezil, a centrally acting cholinesterase inhibitor, on cognitive performances, motor function and daily living activities in progressive supranuclear palsy (PSP). MATERIALS AND METHODS: Six patients with a diagnosis of PSP were evaluated at baseline and after 3 months of treatment with donepezil, 10 mg given at bedtime. Cognitive functions, motor symptoms and daily activities were evaluated by means of appropriate rating scales. RESULTS: Donepezil was not effective on cognitive dysfunction and did not change ratings of daily living. Parkinsonian symptoms were unaffected by donepezil treatment. CONCLUSIONS: Cholinergic replacement therapy alone is not likely to improve symptoms in a disorder characterized by a more widespread impairment of monoaminergic systems. Larger studies may be necessary to confirm the lack of effect of donepezil in this disorder.
AIMS: Patients with atrial flutter are believed to be at lower risk of thromboembolism than patients with atrial fibrillation. However, the incidence of atrial thrombi and the need for anticoagulation in patients with atrial flutter is not well established. METHODS AND RESULTS: A prospective observational multicentre study was undertaken to assess the frequency of atrial thrombi and spontaneous echocontrast and the prevalence for aortic complex atherosclerotic lesions in a cohort of unselected patients with atrial flutter. We evaluated 134 patients (102 male, aged 70+/-9 years); exclusion criteria were history of atrial fibrillation, rheumatic mitral valve disease and mitral mechanical prosthesis. The median of atrial flutter duration was 33 days. Twelve patients had been taking warfarin for more than 7 days. One hundred and twenty-four patients (94%) underwent a transoesophageal echocardiogram, which revealed left atrial appendage thrombi in two patients (1.6%) and right atrial thrombi in one patient (1%). At least moderate left atrial echocontrast was found in 16/124 patients (13%). Complex atherosclerotic aortic plaques were detected in 10 patients (8%). Atrial flutter conversion was attempted in 93/134 patients (69%). At the 1-month follow-up, two patients experienced a thromboembolic event following restoration of sinus rhythm. CONCLUSIONS: Atrial thrombi and echocontrast, and complex aortic atherosclerotic plaques are relatively uncommon in patients with atrial flutter. Post-cardioversion embolism was observed in two patients in our study population.
BACKGROUND: The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. METHODS AND RESULTS: Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). CONCLUSIONS: At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.
Recently, some case-control studies and case reports have shown an association between solvent exposure and parkinsonisms. We present a 55-year-old male parkinsonian patient with chronic exposure to n-hexane for 17 years. The results of neurophysiological (electromyography, evoked potentials), neuroradiological (MRI) and neuropsychological tests performed on the patient suggest a role of this solvent at the level of the central nervous system. Biological susceptibility to neurotoxic compounds is discussed briefly.