Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study.

BACKGROUND AND PURPOSE: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. METHODS: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. RESULTS: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary end-point: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 ± 2.9 to 8.9 ± 1.8; P = 0.27). CONCLUSION: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Effects of testosterone on the Q-T interval in older men and older women with chronic heart failure.

The Q-Tc interval duration on the electrocardiogram is recognized to differ between the sexes. In vitro data and data from humans before and after puberty and menopause suggest that sex hormones play a role in the longer Q-Tc intervals in women, or conversely, the shorter Q-Tc intervals in men. Direct investigations of sex hormone effects on the Q-Tc interval in humans, however, are limited and reach conflicting conclusions. Our objective was to determine effects of testosterone on ECG Q-T intervals of older men and older women. ECG's from 84 older men and older women in double-blind placebo-controlled investigations of testosterone supplementation for the treatment of chronic heart failure (CHF) were analysed. Thirty men received 1000mg intramuscular long-acting testosterone undecanoate and 28 men received saline at 0, 6 and 12weeks. ECG's were recorded at baseline and 12weeks. Sixteen women received transdermal testosterone (33µg) and 10 women received matching placebo twice weekly for 24 weeks with ECG's at baseline and after 24weeks. Testosterone, but not placebo, shortened Q-T and Q-Tc intervals without heart rate changes. Q-T intervals decreased from 385±28 (mean±SD) to 382±28 ms (p<0.002) and Q-Tc intervals decreased from 398±26 to 392±27 (p<0.006) in men on testosterone. In women, Q-T intervals decreased from 400±25 to 397±23ms (p=0.06) and Q-Tc intervals from 415±26 to 409±27ms (p=0.3) on testosterone. Q-T intervals were longer in women compared with men under all conditions (p<0.03). The data support a direct effect of testosterone to shorten Q-T intervals in older men and older women in the absence of HR changes or hypogonadal status. Mean decreases are small and unlikely to affect risks of arrhythmic events in patients receiving Q-T prolonging medications.

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre.

BACKGROUND: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups METHODS: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. RESULTS: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, alpha fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. CONCLUSIONS: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

[Abbreviated laparotomy in patients with hemorrhagic shock]. / La laparotomia abbreviata in pazienti con shock emorragico.

Five cases of severe hemorrhagic shock of abdominal origin treated with abbreviated laparotomy due to the onset of hypothermia, acidosis and consumption coagulopathy are described. The abdomen was temporarily closed and the patients were transferred to these Intensive Therapy Unit for the treatment correction of these disorders. Patients were then re-operated on 30 hours after the reestablishment of vital functions. Clinical complications of hemorrhagic shock, in which the "Abbreviated Laparotomy" technique is applicable, are presented.

[Ludwig angina: a disease of the past century. Case report]. / Angina di Ludwig: una malattia del secolo passato. Descrizione di un caso clinico.

The case of a patient with Ludwig's angina, diffuse inflammation of the submandibular and sublingual spaces, a rare but life threatening disease, is described. This disorder can develop almost always as a complication of the dental infection. Causative bacteria include many Gram-negative, anaerobic organisms, streptococci and staphylococci. The potential for rapid respiratory obstruction is the greatest concern. Other serious complications include sepsis, mediastinitis, pleural empidema, pericarditis, pericardial tamponade. A cervico thoracic CT-scan and neck RNM, were performed to determine the extent of the inflammatory lesion. Treatment consists of ensuring adequate ventilation, with tracheostomy, broad spectrum antibiotic therapy and surgical drainage of the source of infection. The patient recovered without complications.

An apparent idiopathic case of relapsing acute pancreatitis.

We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.

Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to the newly discovered hypotensive peptide, adrenomedullin, were compared with responses to the structurally related peptides, calcitonin gene-related peptide (CGRP) and amylin, in the intact-chest cat. Under conditions of controlled blood flow, when tone in the pulmonary vascular bed had been raised to a high steady level, intralobar injections of adrenomedullin (0.03-1 nmol), CGRP (0.1-3 nmol), and amylin (0.1 and 0.3 nmol) caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. In terms of relative vasodilator activity in the pulmonary vascular bed, the dose of the peptide that decreased lobar arterial pressure 7.5 mm Hg (ED7.5 mm Hg) was significantly lower for adrenomedullin than for CGRP. The duration of the pulmonary vasodilator responses to CGRP was longer than for adrenomedullin, and both peptides decreased systemic arterial pressure when injected into the perfused lobar artery in the higher doses studied. The present data demonstrate that synthetic human adrenomedullin and CGRP have potent but relatively short-lasting vasodilator activity in the pulmonary vascular bed. These data show also that amylin, a structurally related pancreatic peptide, also has significant pulmonary vasodilator activity.

[Acute voluntary poisoning with propafenone. A clinical case]. / Intossicazione volontaria acuta da propafenone. Caso clinico.

Propaphenone hydrochloride in an antiarrhythmic which belongs to class 1C. In recent years it has been widely used in clinical medicine, mainly in the treatment of hyperkinetic arrhythmia. Given the enormous quantity of the medication taken, the description of the case seemed opportune as well as that of the clinical manifestations and electrocardiographic modifications linked to the parmakinetic and electrophysiological characteristics.

[Sudden death in athletes]. / La mort subite chez l'athlète.

In France, about one of ten thousand athletes die suddenly each year. Although this is a small proportion of the number of total deaths, it is a striking one because of the subjects it concern e.g: healthy and physically trained. Age is the major determinant cause of sudden death: coronary heart disease in victims over 35 years, hypertrophic cardiomyopathy, congenital disease and aortic rupture before. Positive predictive value of usual tests is given; high value of echocardiography is to be noted, in comparison with low value of the traditional stress test for detection of subjects at risk.

In vitro rheological assessment of mucolytic activity induced by seaprose.

Proteolytic enzymes can act on the polymeric structure of the bronchial mucus, shortening the long chain of mucoproteins, DNA and other macromolecules, and thus reducing the viscosity of the mucus facilitating its expectoration. Seaprose (Flaminase, Puropharma) belongs to this class and is a proteinase from Aspergillus melleus and it is mainly used in traumatology, orthopaedics, gynaecology and pneumology. In the present study the in vitro activity of increasing concentrations (0.25, 0.5, 1%) of seaprose incubated with bronchial mucus samples (1 ml) was investigated by a rheological technique (transient test) that assesses changes in viscosity and elasticity. A dose-effect relationship between increasing concentrations of seaprose and the corresponding reductions in bronchial mucus viscosity was found. There was also a parallel reduction in elasticity after incubation with 0.5%, but an unfortunate distribution of values for 0.25 and 1% concentrations does not allow us to state whether there is a dose-effect relationship for elasticity.

Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation.

The topical tolerability of an intranasal salmon calcitonin spray preparation, of the excipients alone and of sodium taurocholate has been studied by assessment of the mucociliary transport velocity (MTV) on the frog's palate. The rate of mucus transport was investigated in 3 groups of animals (Rana esculenta; 6 frogs per group) in basal conditions and after a challenge with a salmon calcitonin intranasal spray preparation, with the excipients and with sodium taurocholate, respectively. The salmon calcitonin intranasal spray preparation and the excipients did not affect the mucociliary transport velocity on the frog's palate. On the contrary, sodium taurocholate produced severe impairments in the mucociliary transport velocity and histological lesions of the epithelial layer of the frog's palate. The comparison among the mean values of the mucociliary transport velocity before and after treatments showed a significant difference between controls and sodium taurocholate groups (p less than 0.05) as well as among the groups treated with sodium taurocholate versus salmon calcitonin and versus the excipients alone of the calcitonin preparation (p less than 0.05). These findings provide evidence that the salmon calcitonin intranasal spray preparation tested in the present ex vivo model does not affect the mucociliary transport velocity in the frog's palate, while this is markedly affected by sodium taurocholate. The use of sodium taurocholate as a promoter of absorption in intranasal preparations should thus be reconsidered.

[Cannulation of the subclavian vein using the subclavicular route: technic of choice for fluid therapy and prolonged total parenteral feeding]. / L'incannulamento della vena succlavia per via sottoclaveare. Metodica di scelta per la fluidoterapia e l'alimentazione parenterale totale prolungata.

The various routes to the large veins and the technique for placing a long-term plastic catheter for fluid therapy and prolonged total parenteral feeding, are described with respective limitations and contraindications. It is considered that cannulation of the subclavian vein by the subclavicular route using Cavafix instrumentation is preferable because it is comparatively easy to carry out complications are limited, and scrupulous asepsis is possible. It can also be applied in any patient even in the most serious of conditions without having to make him take up a special position.