Quantifying the relationship between disability progression and quality of life in patients treated for NMOSD: Insights from the SAkura studies.

BACKGROUND: To date, no specific scales have been developed to explore the impact of neuromyelitis optica spectrum disorder (NMOSD)-related disability on quality of life (QoL). The Expanded Disability Status Scale (EDSS) and the EuroQol 5-dimensions (EQ-5D) have been used to assess disability and QoL, respectively, in patients with NMOSD. However, there is limited evidence surrounding their use in this condition. We compared EDSS and EQ-5D data across two clinical trials to quantify the relationship between disability and QoL in patients with NMOSD. METHODS: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) were Phase 3, multicenter, randomized, international, double-blind, placebo-controlled, parallel-assignment studies of satralizumab, administered in combination with baseline immunosuppressants (SAkuraSky) or as monotherapy (SAkuraStar). EDSS and EQ-5D were assessed at baseline and at 24-week intervals thereafter. The relationship between disability and QoL was assessed by estimating EQ-5D utilities (UK tariff) for each incremental EDSS category. A repeated-measures linear model was used to regress health utilities on EDSS score-derived health states. RESULTS: Overall, 176 patients underwent at least one EDSS assessment and completed an EQ-5D survey and were included in this analysis. There was a clear association between mean EQ-5D score and EDSS score, with decreases in QoL being observed at each incremental increase in disability. The relationship between EDSS and EQ-5D score remained consistent across the different treatment groups. CONCLUSIONS: These results, generated from high-quality clinical trial data, demonstrated a strong and consistent relationship between disability and QoL in patients with NMOSD.

Experimental validation of a newly designed 6 degrees of freedom scanning laser head: application to three-dimensional beam structure.

A new scanning laser head is designed to use single Laser Doppler Vibrometer (LDV) for performing measurements up to 6 degrees of freedom (DOF) at a target. The scanning head is supported by a rotating hollow shaft, which allows the laser beam to travel up to the scanning head from an opposite direction where an LDV is set up. The scanning head is made of a set of two mirrors, which deflects the laser beam with an angle so that the rotation of the scanning head produces a conical scan. When measurements are performed at the focal point of the conical scan then three translational vibration components can be measured, otherwise the very small circle scan, before and after the focal point, can measure up to 6 degrees of freedom, including three translations and three rotations. This paper presents the 6DOF scanning head and the measurements of 3D operational deflection shapes of a test structure.

High-order behaviour in learning gate networks with lateral inhibition.

In this work we present a neural network model incorporating activity-dependent presynaptic facilitation with multidimensional inputs. The processing unit used is based on a slightly simplified version of the Learning Gate Model proposed by Ciaccia et al. (1992). The network topology integrates a well-known biological neural circuit with a lateral inhibition connection subnet. By means of simulation experiments, we show that the proposed networks exhibit basic and high-order features of associative learning. In particular, overshadowing and blocking are reproduced in the presence of both noise-free and noisy inputs. The role of noise in the development of high-order learning capabilities is also discussed.

Cortical kidney scan evaluation in the follow-up of children with vesico-ureteric reflux.

We present the results obtained in the follow-up of 66 children with vesico-ureteric reflux (VUR) of different grades (111 refluxing renal units, RU; the VUR being bilateral in 47 children), employing the renal cortical agent 99mTc-aprotinin (TcA). Together with the visual inspection of the scan, we adopted a quantitative approach, expressing the results as the split percent uptake of the injected dose. The detection of morphological anomalies was more frequent in the cases of more severe reflux. Scars were noted in 38 RU, with a higher prevalence in more severe grades, except for grade V where severe impairment was more frequent. With regard to the amount of functioning parenchyma, the probability of a significant loss of nephrons (expressed by a low uptake of TcA), rose with the grades, although the higher grades were not invariably associated with parenchymal failure. The abnormality detection rate is higher by about 2:1 with the TcA scan than with other diagnostic modalities such as i.v. pyelography or echography. No differences were found between RU with or without scars as regards evolution over time; only when the TcA uptake at presentation was lower than 10% was the normal development of the RU likely to be hindered. From these data it can be concluded that early diagnosis is the key factor in the management of these children with VUR; the morpho-functional assessment with TcA uptake is probably the most effective technique for the detection of parenchymal abnormalities. In addition, the test has a high prognostic value, an uptake lower than 10% indicating an unfavourable prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium ratio, phospholipids and the incidence of side effects.

The main aims of our Lithium Centre, which has been operating since 1985, are as follows: 1. the treatment of affective disorders and particularly the recurrent ones; 2. the emphasis of the Li-ratio as a predictive index of therapeutic effects on the one hand, and of the appearance of side effects on the other hand; 3. the prevention and pharmacological control of side effects and research about their mechanism of arising.; 4. organization of a computerized bibliographic service.

Incidence of coronary thrombosis in sudden death due to coronary artery disease.

Acute coronary thrombosis does not play a major role in the causation of sudden unexpected death due to coronary artery disease. In a study of 500 consecutive autopsies of individuals aged 20-99 years, dying suddenly and unexpectedly of coronary artery disease, only 67 (13.4%) showed an acute thrombosis. In contrast, studies of hospitalized patients with acute transmural infarction of the myocardium showed a rate of coronary artery occlusion > 80%.

An analytical short- and long-term memory model of presynaptic plasticity.

A mathematical model, called the Learning Gate Model (LGM), that describes phenomena responsible for biological synaptic plasticity, is presented. The functionality of the model are mainly based on the work of Kandel and colleagues on the most elementary forms of learning observed in the Aplysia Californica marine mollusc. In particular, emphasis is placed on the double temporal dynamics of synaptic plasticity and the temporal specificity of classical conditioning. By properly modeling the effect of the binding of Ca++ ions to the serotonin-sensitive adenylate cyclase enzyme, it is shown how a positively accelerated learning curve can be obtained for sensitization and classical conditioning. Phenomena of spontaneous recovery and second-order conditioning are reproduced through simulations. Mathematical analyses of the temporal trace of conditioned stimulus and of the Short-Term Memory steady state are also given.

Natural death as viewed by the medical examiner: a review of 1000 consecutive autopsies of individuals dying of natural disease.

A study of 1000 consecutive autopsies of individuals dying of natural disease was conducted. Cardiovascular disease was responsible for 60.9% of all deaths with coronary artery disease--not only the main cause of cardiovascular death but also the main cause of all natural deaths--accounting for 45.1% of such cases. Diseases of the central nervous and respiratory systems accounted for 8.7 and 8.6%, respectively, of the natural deaths. Seizure disorders and pneumonia were the main causes of death in these organ systems. There were 124 deaths of children less than one year in age, 91 of which were due to sudden infant death syndrome (SIDS). All of the SIDS deaths were in children less than 10 months old.

Lithium-TCA induced malignant syndrome. Case report.

1. The authors describe some adverse reactions, induced by lithium and TCA administration, in a 71 years old woman treated for mixed bipolar disturbance. 2. The case history here described, is perfectly compatible with a diagnosis of Malignant Hyperthermia (MH). 3. Utility of the association of hypothalamic phospholipid liposomes (HPL) and myorelaxants in the reduction of these lithium side effects, is discussed.

[Angiopathy caused by vibrating tools: cold test and prostaglandin balance]. / Angiopatia da vibranti: cold test e bilancia prostaglandinica.

A study was made on a group of workers occupationally exposed to tools producing medium-to-low frequency vibrations, and on a comparable control group. The subjects underwent a plethysmographic examination with the cold test, which revealed a greater number of sphygmic alterations in the exposed group; at the same time spontaneous platelet aggregation, blood levels of 6-K-PGF-1 alpha and TXB2 and urinary levels of BTGU were determined in basal conditions and after the cold test. Except for the slight, and not statistically significant, increase in TXB2, the results did not reveal any alterations in the constituents of the prostaglandin balance after the cold test. This therefore indicates that biohumoral changes of this type were not involved in producing cold-induced vasomotor alterations in the group under study. However, further investigations are recommended which will take account of the age and working history of the subjects, and particularly of the physical characteristics of the vibrations produced by the tools used, especially the Hz number.

[Type A behavior and cardiovascular reactivity. Preliminary findings]. / Tipo comportamentale "A" e reattività cardiovascolare. Rilievi preliminari.

In view of reports of a connection between ischaemic cardiopathies and "A" type behaviour, the response of certain cardiocirculatory parameters to given physical stimuli was investigated in a group of people doing high stress work. The data did in fact reveal a tendency to more pronounced cardiovascular reactivity in the A group, a difference that was statistically significant in the cold pressor and cold tests. The possible links between enhanced vasomotor response and increased risk of coronary heart disease are pointed out with emphasis on recent hypotheses about the possible pathogenic role of enhanced 5-OH-tryptamine release and particular alterations in the alpha/beta adrenergic receptor balance.

[Spontaneous platelet aggregation after experimental focal ischemia in the rabbit. "Sensitivity", "specificity" and value of the test used]. / Considerazioni sull'aggregabilità piastrinica spontanea dopo ischemia focale sperimentale nel coniglio. "Sensibilità", "specificità" e validità del test impiegato.

Within the framework of an investigation at present under way at the Neurological Clinic of Pavia on experimental focal ischaemia, the peculiarities of platelet aggregation observed, have led to a more accurate assessment of both the phenomenon itself and the validity of the method used. In a group of 30 rabbits (17 of them submitted to embolization by means of microspheres introduced into the carotid and 13 used as controls), biohumoral electrical and histological parameters were examined. The spontaneous platelet aggregation test proved significantly related to the extent of changes taking place, as measured by PDS levels and QEEG "delta" activity (respectively, P less than 0.005 and P less than 0.05). Platelet aggregation, in relation to the occurrence or absence of focal ischaemia, revealed a "sensitivity" of 80% and a "specificity" of 92.3%. When not only the onset of but also the increase in aggregation is taken into account, the "sensitivity" figure appears to go up to 93.3%. Endothelial damage and "cascade" platelet aggregation appeared to be a prerequisite for the occurrence of the changes found. In these changes, the pathogenetic role of the regional vasospasm as opposed to mere mechanical obstruction seems to be confirmed. On the basis of these findings, it is concluded that the identification of spontaneous platelet aggregation using K. Breddin's method and its quantification based on Born's turbidimetric principle, may be usefully employed to assess the risk factor constituted by an abnormal tendency to platelet hyperaggregation.

Clinical notes on buspirone.

The main aspects of the recent development of non-benzodiazepine anxiolytic drugs are the following: the possibility of giving drugs with peculiar anxioselective profile and with no benzodiazepine side-effects; the possibility of discriminating the anxiolytic from the hypnotic activity; the possibility of a nosographic delimitation: buspirone is used mainly in the treatment of generalized anxiety disorders. All these factors point to the possibility of a guided or planned anxiolysis with a more active participation from the patients.

Notes on human behavioural pharmacotoxicology.

1. After 30 years of psychopharmacological therapy we are able to identify some aspects which can be referred to a "collateral behavioural effect". The apparent rarity of this depends on the facility of confusing behavioural modifications (often sine materia), with patological ones (normally of a physical nature). 2. Memory, learning, the ability of evoking, problems regarding reality, paradoxical reactions, "makefobic" behaviour, passivity and social and behavioural withdrawal, form part of the Human Behavioural Pharmacotoxicology. 3. This ought to deserve greater attention on the part both of research workers and health authorities.

[Cardiocirculatory findings in a group of workers exposed to nitro derivatives. A pathogenetic hypothesis of withdrawal hazard]. / Rilievi cardiocircolatori in un gruppo di lavoratori esposti a nitroderivati. Una ipotesi patogenetica del "withdrawal hazard".

After briefly recalling the professional pathology characteristics of workers exposed to nitro derivatives and the perplexities surrounding the actual pathogenetic mechanism of the "Withdrawal hazard", the AA report the results of an investigation carried out among the workers of a dynamite producing plant. In the study, the NG and EGDN environmental levels were checked and the workers were submitted to ECG tracings, ECG D according to Holter, and monitoring of postural pressure changes both during exposure to the substances and during time-outs. The results obtained showed that the concentrations found in the plant were practically within the recommended TLV values, with no pathological modifications of the parameters examined. The AA put forward a pathogenetic hypothesis based on these findings and analyzing epidemiologic data on coronary sudden death as well as the mechanisms regarded as responsible for the disorders described in the literature in professionally exposed subjects. According to such hypothesis, the "Withdrawal hazard" (if any) would not be due to the cessation of the vasodilation effect of the nitro derivatives but would be a "rebound" phenomenon following the NG - and EGDN - inhalation induced stimulation to the production of endothelial prostaglandins, and of EDRF in particular, in exposed workers. The withdrawal of nitro derivatives inhalation would thus eliminate a vascular and coronary protection mechanism in the case of pathogenetic noxae at cardiovascular level. Such an interpretation would at last account for the time elapsing between cessation of work and occurrence of the disorders, which would not be justified by the cessation of the mere vasodilating action, since this wears out within a few hours.(ABSTRACT TRUNCATED AT 250 WORDS)