Impact of an early respiratory care programme with non-invasive ventilation adaptation in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Forced vital capacity (FVC) <80% is one of the key indications for starting non-invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). It was hypothesized that a very early start of NIV could lengthen the free interval before death compared to later-start NIV; as a secondary outcome, the survival rate of patients on NIV without tracheotomy was also evaluated. METHODS: This retrospective study was conducted on 194 ALS patients, divided into a later group (LG) with FVC <80% at NIV prescription (n = 129) and a very early group (VEG) with FVC ≥80% at NIV prescription (n = 65). Clinical and respiratory functional data and time free to death between groups over a 3-year follow-up were compared. RESULT: At 36 months from diagnosis, mortality was 35% for the VEG versus 52.7% for the LG (P = 0.022). Kaplan-Meier survival curves adjusted for tracheotomy showed a lower probability of death (P = 0.001) for the VEG as a whole (P = 0.001) and for the non-bulbar (NB) subgroup (P = 0.007). Very early NIV was protective of survival for all patients [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.28-0.74; P = 0.001] and for the NB subgroup (HR 0.43; 95% CI 0.23-0.79; P = 0.007), whilst a tracheotomy was protective for all patients (HR 0.27; 95% CI 0.15-0.50; P = 0.000) and both NB (HR 0.26; 95% CI 0.12-0.56; P = 0.001) and bulbar subgroups (HR 0.29; 95% CI 0.11-0.77; P = 0.013). Survival in VEG patients on NIV without tracheotomy was three times that for the LG (43.1% vs. 14.7%). CONCLUSION: Very early NIV prescription prolongs the free time from diagnosis to death in NB ALS patients whilst tracheotomy reduces the mortality risk in all patients.

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis.

Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels - as occurring in schizophrenia - may contribute to the pathology through an effect on postsynaptic function and plasticity.

Translational and rotational temperatures of a 2D vibrated granular gas in microgravity.

We present an experimental study performed on a vibrated granular gas enclosed into a 2D rectangular cell. Experiments are performed in microgravity conditions achieved during parabolic flights. High speed video recording and optical tracking allow to obtain the full kinematics (translation and rotation) of the particles. The inelastic parameters are retrieved from the experimental trajectories as well as the translational and rotational velocity distributions. We report that the experimental ratio of translational versus rotational temperature decreases with the density of the medium but increases with the driving velocity of the cell. These experimental results are compared with existing theories and we point out the differences observed. We also present a model which fairly predicts the equilibrium experimental temperatures along the direction of vibration.

The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.

The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P < 0.05), whereas 10-OH-CZ half-lives were only marginally shorter (17 +/- 1 h vs 20 +/- 2 h, NS). These data indicate that the biotransformation of OXC and 10-OH-CZ may be accelerated by concomitant treatment with phenobarbitone but that the magnitude of this effect is unlikely to be of great clinical significance.

Daytime sleepiness in epileptic patients on long-term monotherapy: MSLT, clinical and psychometric assessment.

A multiparametric investigation of daytime sleepiness was carried out in 10 patients with a generalized epilepsy treated by phenobarbital, 10 with a cryptogenic partial epilepsy treated by carbamazepine and 10 healthy controls. After a standard ambulatory night-time polysomnography, an objective and subjective estimate of daytime sleepiness was made in each subject by means of the Multiple Sleep Latency Test (MSLT) and visual analogue rating scale (VARS), respectively. Furthermore, a parallel assessment of mood and cognitive tasks involving attention and psychomotor speed was also carried out. The data show that patients on chronic treatment with phenobarbital have a greater daytime sleep tendency and they show a worse score at the digit symbol substitution test, than patients on carbamazepine and healthy controls.

Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy.

Twenty-five patients with epilepsy (mostly with partial seizures) who had responded favourably to a short-term trial of add-on vigabatrin entered maintenance treatment. After 52 to 78 months, 15 patients continue to take the drug with good therapeutic response. Median monthly seizure frequency during the last 2 months on vigabatrin in all patients, including drop-outs, was 3.5 (range 0-74) as compared with 10 (range 3-98) during an initial placebo period (p < 0.01). Drop-outs were caused by adverse events in 2 cases (ataxia and psychotic symptoms respectively), seizure breakthrough in 4 cases and reasons unrelated to treatment in 4 patients. In most patients, side effects were absent or mild, the most frequent complaint being weight gain. It is concluded that the antiepileptic efficacy and good clinical tolerability of vigabatrin are generally maintained during long-term treatment for up to 6 years.

[Hemorrheological changes in peripheral obliterative arterial diseases]. / Le alterazioni emoreologiche nell'arteriopatia obliterante periferica.

The relationships between blood rheology and peripheral arterial disease are reviewed. The connections between abnormal blood rheology and peripheral arterial disease are discussed considering the opinions of the enthusiastic and skeptic rheologists. A prospective for future investigations is also proposed.

[Relation of blood viscosity, plasma viscosity and hematocrit]. / Rapporti fra viscosità ematica, viscosità plasmatica ed ematocrito.

The results from 398 consecutive measurements of blood viscosity, plasma viscosity and hematocrit were submitted to a statistical analysis. Hematocrit appeared to be the main determinant of blood viscosity, even though its influence was not so strong as illustrated in previous investigations. The correlation between blood viscosity and hematocrit appeared strictly connected with the red cell amount of the blood sample, being higher when the latter exceeded its physiological range; this correlation disappeared when red blood cell amount was strongly reduced, while the correlation between plasma viscosity and blood viscosity had an opposite behaviour. From these results we can conclude that correlations between hematocrit and plasma viscosity with blood viscosity have opposite trends and that a reciprocal interference is often present.

[A small subpopulation of rigid erythrocytes changes the erythrocyte filtration test]. / Una piccola sottopopolazione di emazie rigide altera il test della filtrazione eritrocitaria.

By means of the filterability test of Reid et al., the influence of a subpopulation of rigid erythrocytes (5% and 2.5%, respectively) was studied using Nucleopore polycarbonate membranes with pore size of 5 mu and diameter of 13 mm. The addition of 5% and 2.5% of rigid red cells delays the erythrocyte filtration times and alters the red cell deformability index. The meaning of the obtained data is discussed.

[The lack of correlation between erythrocyte filtration parameters and other hemorrheological parameters]. / Sulla non correlazione fra parametri della filtrazione eritrocitaria ed altri parametri emoreologici.

The findings of 300 consecutive measurements of erythrocyte filterability, whole blood viscosity, plasma viscosity, hematocrit, mean corpuscular volume and white blood cell count have been statistically analyzed in order to find a possible correlation between these parameters. No correlation between erythrocyte filterability, whole blood viscosity, plasma viscosity, hematocrit, mean corpuscular volume and white blood cell count was found. Some hypotheses are enunciated to explain such absence of correlation. The meaning of erythrocyte filtration test is still unclear.

[Hemorrheological changes induced by submaximal exertion in subjects with insulin-dependent diabetes mellitus]. / Modificazioni emoreologiche indotte da uno sforzo submassimale in soggetti con diabete mellito insulinodipendente.

The influence of an acute physical exercise on hemorheological parameters in insulin-dependent diabetes mellitus in not actually known. We have examined the behavior of hemorheological parameters and other laboratory findings such as blood glucose, blood lactic acid, O2 and CO2 venous pressure and venous pH before and after a submaximal physical exercise standardized by ECG monitoring and by means of an 'oxygen consumption computer'. The work load was significantly lower in diabetic patients than in normal control subjects. On the other hand, changes in hemorheological parameters were more evident in diabetic patients. The significance of these findings is also discussed.