Influence of lisuride on morphine withdrawal signs in the rat: A dopamine-mimetic effect

The influence of lisuride on naloxone-induced withdrawal signs (wet shakes, escape attempts) was studied in morphine-dependent rats. Lisuride, injected IP at doses of 12.5 and 25 g/kg, inhibited wet shakes while not significantly altering escape attempts induced by naloxone (4 mg/kg IP). At higher doses (50 and 100 g/kg IP), lisuride's inhibitory effect on wet shakes persisted while escape attempts were actually potentiated with respect to control withdrawal rats. Increases in aggressive behavior were seen at all doses, and were dose-related. Haloperidol (0.3 mg/kg IP), administered 40 min before lisuride, did not modify the antagonistic effect on wet shakes, unlike sulpiride (40 mg/kg IP 30 min before lisuride), but at the same time blocked the increase in escape attempts and aggressiveness induced by lisuride. We suggest that lisuride modulates withdrawal signs by stimulation of dopamine receptors in the CNS. The effect of the dopamine mimetic N-n-propylnorapomorphine (NPA) on the same variables is reported as well as the influence of haloperidol on NPA, and a comparison between the effects of the two drugs is made.     

Effects of prefrontal repetitive transcranial magnetic stimulation on the autonomic regulation of cardiovascular function

Several protocols based on repetitive transcranial magnetic stimulation (rTMS) have been proposed for treatment of a variety of neurological disorders. Despite the widespread use, little is known about the effects of rTMS on the autonomic nervous control of the cardiovascular system. Twelve volunteers underwent rTMS sessions consisted in 8-min baseline recording, 8-min 0.7-Hz rTMS stimulation at 100 % of the motor cortex excitability threshold on the prefrontal cortex of one randomly assigned hemisphere. After 8-min recovery, the same procedure was performed on the contra-lateral hemisphere. Non-invasive (Portapres device) beat-by-beat blood pressure and heart period time series were recorded and analyzed by spectral and cross-spectral analysis in the low-frequency (LF ≈ 0.1 Hz) and in the high-frequency (HF = respiratory frequency) range. Repetitive TMS, particularly after stimulation of the right hemisphere, induced a slight increase in the parasympathetic drive and no effects on the sympathetic activity. There was a significant bradycardia after stimulation on the right hemisphere, not significant bradycardia after left stimulation. LF/HF ratio was 3.8 ± 2.1 during baseline and changed to 1.9 ± 0.6 during rTMS on the left and to 1.6 ± 0.6 during rTMS on the right. No significant changes were observed in blood pressure. Low-frequency rTMS of the prefrontal cortex induces a slight parasympathetic activation and no changes in the sympathetic function.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

Improved survival in limited scleroderma-related pulmonary artery hypertension

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO₂) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO₂ <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO₂ are predictors of survival and may assist in planning treatment.     

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95 % confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4 %) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95 % CI 1.61–21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.     

The need of a hybrid approach for the treatment of atrial fibrillation

Atrial fibrillation represents nowadays one of the most important burdens in the field of arrhythmia. Albeit often inadequate, medical treatment is still considered the "first-step" approach. Non-pharmacological strategies, either surgical or interventional, recently gained an increasing interest among both cardiac surgeons and electrophysiologists. From the surgical standpoint, the introduction of different energy sources and the development of minimally invasive techniques as an alternative to the original "cut-and-sew" technique allowed a new dawn in the surgical treatment of atrial fibrillation. In the meanwhile, electrophysiologists developed more complex ablation systems that allowed the creation of linear lesions, similar to the surgical ones, while mapping the atria with three-dimensional (3D) navigation systems. Nevertheless, the success rate in terms of sinus rhythm restoration was around 80%-85% in both fields. We foresee that the combination of the two approaches (i.e., surgical and percutaneous approach), in common hybrid approach, will allow a substantial reform for the definitive cure of atrial fibrillation, either paroxysmal or permanent, providing the highest success rates along with the best care for patients' health.     

Cross-spectral analysis of cardiovascular parameters whilst supine may identify subjects with poor orthostatic tolerance

An easy and low-cost method for identification of subjects prone to orthostatic vasovagal syncope would be of clinical benefit. An orthostatic test with 60 degrees head-up tilt and progressive lower-body negative pressure was performed on 79 patients with histories of unexplained syncope and 26 control subjects. The test was stopped at the onset of presyncope and time to presyncope was taken as a measure of orthostatic tolerance. Spectral and cross-spectral analysis was performed on the supine time series of the R-R interval (ECG) and systolic pressure (Finapres) recorded before the beginning of the test. According to reference values, 38 patients and 11 controls were classified as having poor orthostatic tolerance (PPT and CPT respectively), whereas 41 patients and 15 controls displayed normal orthostatic tolerance (PNT and CNT respectively). The central frequency of the low-frequency (LF approximately equal to 0.1 Hz.) oscillations in PNT and CNT was significantly higher than that in PPT and CPT. In addition, it was significantly linearly correlated with the time of presyncope. Using our test of orthostatic tolerance as a comparison, the LF central frequency allows the classification of subjects with poor or normal tolerance with 80% sensitivity and 82% specificity. These results suggest that the LF central frequency in the supine position may provide a useful index in the diagnosis of orthostatic intolerance.     

Social cognition and atypical antipsychotic agents in the treatment of persons with schizophrenia: preliminary data from a naturalistic study

Schizophrenia is a chronic disorder that begins in adolescence or in early adulthood. In schizophrenic disorder there are relevant deficits in social interaction. The aim of this study was to evaluate the efficacy of atypical antipsychotic drugs compared to a conventional antipsychotic in the treatment of psychotic symptoms and on cognitive functions of a group of people affected by schizophrenia. Effects of novel antipsychotic drugs on social functioning improvement, regarded as improvement in the ability to represent mental states, were thoroughly assessed. Our study was conducted in the form of naturalistic observation of a sample of 45 people affected by schizophrenia treated with haloperidol, clozapine and risperidone. Our results show that after one year of treatment there were significant positive results in social competence abilities in the group of people being treated with risperidone. Theses results may have a relevant impact on the improvement of quality of life in people affected by schizophrenia.