Correction to: A case of intracoronary and endovenous levosimendan as a rescue therapy for refractory cardiac arrest.

After publication of this supplement [1], it was brought to our attention that the author 'L. Vegnuti' has been erroneously omitted from the author list of the following abstract.

Aldosterone receptor antagonism and heart failure: insights from an outpatient clinic.

OBJECTIVE: In randomized clinical trials, aldosterone antagonists have been shown to reduce mortality and morbidity in heart failure (HF). The aim of the present study was to examine the risk-benefit profile of aldosterone antagonists in routine clinical practice. METHODS: A retrospective analysis, extending over a 1-year period, of the clinical, instrumental and laboratory data of 264 HF outpatients was performed. All patients were on a beta-blocker and an ACE-inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone antagonist. RESULTS: At baseline, subjects treated with aldosterone antagonists had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse ejection fraction and a higher systolic pulmonary arterial pressure (sPAP). During follow-up, a greater reduction in sPAP and a tendency towards improved systolic and diastolic function were observed in subjects treated with aldosterone antagonists. Moreover, clinical and laboratory parameters did not deteriorate in patients taking aldosterone antagonists. Mortality rates were similar in the two groups (8.6% vs. 8.8%, P = NS). CONCLUSIONS: The use of aldosterone antagonists in HF is associated with an improvement in cardiac function and is well tolerated. In the present study, patients administered these agents had a comparable clinical outcome to that of the control group, despite important differences in baseline risk.

Latin America: the next region for haematopoietic transplant progress.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid.

Gal beta 1-->3GalN beta 1-->4Gal(3<--2 alpha Neu)beta 1-->4Glc beta-->1Sph (WILD20), a new glycosphingolipid, a breakdown product of the monosialoganglioside GM1 obtained through alkaline hydrolysis, shows dose-dependent platelet anti-aggregating properties in vitro and in vivo. This effect is agonist- and species-independent. The family of lysosphingolipids, to which the compound belongs, is present in platelets particularly after thrombin treatment. WILD20 antiplatelet effect is due to the interference with ADP or thrombin-induced aggregation, probably via phospholipase A2 (PLA2) blockade; the substance is also effective when arachidonic acid is used as an agonist. Serotonin blood levels are also reduced. The substance, orally active at dosages of 0.1-0.01 mg/kg as antiplatelets agent, prolonged bleeding time without interfering with the coagulative or fibrinolytic processes.

Effect of a new de-N-acetyl-lysoglycosphingolipid on some tumour models.

A new de-N-acetylated glycosphingolipid termed WILD20, a breakdown product of GM1 obtained through alkaline hydrolysis, and characterized by nuclear magnetic resonance, mass spectrometry and elementary analysis, was found to inhibit phospholipase A2 via phosphokinase C translocation blockade. The substance inhibited various tumour cell lines in vitro, in synergy with doxorubicin and cisplatin. In vivo, it showed an antitumoral effect when both the tumour cells and WILD20 were injected at the same site (peritoneal cavity). Tumour cells, incubated with WILD20, showed a dose-dependent decrease of oncogenicity without impairment of viability. WILD20 also down-regulated tumour cell adherence to laminin and fibronectin. When peritumorally administered, WILD20 impaired tumour growth and potentiated the peritumoral effects of recombinant interleukin 2. The results obtained merit exploration of the therapeutical possibilities of this agent in human cancer patients.

Improvement of cognitive function by MAO-B inhibitor L-deprenyl in aged rats.

This study evaluated the ability of the selective MAO-B inhibitor, L-deprenyl, to reverse cognitive impairments appearing in aged rats, using the reference memory, Morris Water Maze paradigm. L-Deprenyl significantly improved learning and memory deficits associated with old age in doses of 1.25 and 5 mg/kg PO (escape latency measure) and doses of 1.25, 2.5 and 5 mg/kg PO (path length measure). L-Deprenyl also improved reversal learning impairments in doses of 1.25, 2.5 and 5 mg/kg PO, as expressed by the escape latency measure. The data suggest that L-deprenyl possesses potential cognitive enhancement abilities probably due to an increase in dopaminergic activity.

The term diplegia should be enhanced. Part III: inter-observer reliability of the new rehabilitation oriented classification.

AIM: The aim of this study was to validate a recent classification of gait in children with the spastic diplegic form of cerebral palsy (CP) by checking the reliability of different scorers in assigning subject walking performance to one of the four specific patterns described in the classification. METHODS: The gait patterns of 50 children and adolescents with CP (23 males, 27 females; age range 3-17 years) were selected among patients whose videos were stored in the archives of the Pisa and Reggio Emilia Hospitals. Only video recordings of gait with homogeneous features (duration of at least 90 s, simultaneous recordings on sagittal and frontal views, and other criteria) were taken for examination. The videos were blindly scored using an observational gait scale, at first by two of the authors of the classification system (defined as ''maximum experts''), then by ten expert observers, and finally by 206 professionals of rehabilitation after a one-day training on the classification. Cohen's kappa statistics (k) and intra class correlations (ICC) were calculated. RESULTS: Kappa and ICC indicate an almost perfect agreement both between the two maximum experts and among the ten expert observers. Good results were also obtained in the group of one-day trained scorers. Only a few cases were assigned to the ''unclassified'' category. The profession of the observer (doctor or therapist) and previous knowledge of the classification had no significant influence on reliability scores. CONCLUSION: The results suggest that the proposed classification can be reliably applied, even utilizing short video recordings, to arrange diplegic children into different patterns. Further studies are needed to validate the use of this classification system for clinical and research aims.

[Teratogenic action of Rifaximin in the rat and rabbit and its effect on perinatal development in the rat]. / Azione teratogena del Rifaximin nel ratto e nel coniglio e sua influenza sullo sviluppo perinatale del ratto.

The purpose of this study is to evaluate the teratogenic action and the effect on perinatal development of Rifaximin. Teratogenic action of Rifaximin was studied in the rat and in the rabbit. The drug was administered by gavage during organogenesis period at 50 and 100 mg/kg; idroxyurea and thalidomide were used as teratogenic drugs. The effect on physical and behavioural development of the pups was studied in the rat at 50 and 100 mg/kg during the foetal period and suckling time. The search for malformation of internal organs was carried out on the half of the fetuses fixed according to Wilson; the examination of the skeleton of the other fetuses was carried out according to Dawson. Some parameters of physical and behavioural development were evaluated in the pups. Rifaximin at these dosages has no teratogenic effects and does not influence the psychophysical development of the pups.

Toxic and mutagenic effects of a low molecular weight heparin in rats.

Acute, subacute, chronic toxicity and mutagenicity studies of a new low molecular weight heparin (OP/LMWH) were carried out in rats. The LD50 values resulted lower by i.m. and s.c. route than after i.p. and i.v. administration. OP/LMWH given by subcutaneous route in subacute and in chronic toxicity produced no significant adverse effects at 5 mg/kg, only marginal effects at 10 mg/kg and moderate effects at the dose of 20 mg/kg. In these studies, unfractionated heparin at 10 mg/kg by s.c. route was used for comparison. At 10 mg/kg, heparin presented effects similar to those shown by OP/LMWH at 20 mg/kg. OP/LMWH did not show any mutagenic activity when compared with mutagenic standards.

Fertility study of rifaximin (L/105) in rats.

The influence of rifaximin (L/105) on conception and pregnancy in rats up to F1 progeny was reported. Rifaximin showed a good fertility rate and no dose-related differences in the number of viable or dead fetuses per litter (Fo progeny) up to 100 mg/kg. The number of live or dead pups at birth, pup weight, gestation length and survival of offspring to weaning were not influenced up to the highest dose, 100 mg/kg (Fo-F1 progeny).

Peri- and postnatal, teratology and reproductive studies of a low molecular weight heparin in rats.

The low molecular weight heparin (OP/LMWH) used in these studies elicited no evidence of teratogenicity when administered by subcutaneous route during the period of organogenesis to pregnant rats at doses up to 10 mg/kg/d. In reproductive studies there were no effects on conception or pregnancy in males or females rats at dosages up to 10 mg/kg/d (by s.c. route). In these studies the doses were used that in chronic toxicity had shown unremarkable toxic effects on animals. In teratologic and in peri- and postnatal experiments unfractionated heparin at doses of 1 and 10 mg/kg/d by s.c. route was used for comparison.

Acute, subacute, chronic toxicity and mutagenicity studies of rifaximin (L/105) in rats.

Acute, subacute and chronic toxicity-mutagenicity studies of rifaximin (L/105), a new semisynthetic rifamycin SV antibiotic, were conducted in rats. The oral LD50 value for this species was greater than 2000 mg/kg. Rifaximin given orally to rats up to 6 months produced no evident adverse effects up to 100 mg/kg. The moderate effects noted were probably due to the topical action of the drug. Rifaximin did not show any mutagenic activity when compared with mutagenic standards.

Toxicological evaluations of the benzodiazepine doxefazepam.

1-(2-Hydroxyethyl)-3-hydroxyl-7-chloro-1,3-dihydro-5-(O-fluorophenyl)-2H - 1,4-benzodiazepin-2-one (doxefazepam, SAS 643, Doxans) was investigated in a series of toxicological studies. Oral LD50 values were greater than 2000 mg/kg in mice, rats and dogs, while endoperitoneal LD50 values were 746 and 544 mg/kg in the mice and rats, respectively, and greater than 1000 mg/kg in the dogs. Subacute and chronic studies in rats and dogs evidenced a transient ataxia after administration of the test compound, which was dose-dependent in the subacute experiment, and occurred only at the highest dose in the chronic studies. No pathological findings were registered at necropsy or in microscopic observations, except an increase of liver weight at the highest dosage in the chronic study in the rat. Doxefazepam did not exert any teratogenic effects in rats and rabbits. Moreover in rats it did not alter the reproductive performance. The mutagenic studies did not reveal any mutagenic potential. In the cancerogenicity study in rats doxefazepam did not show positive carcinogenic potential.

Carcinogenicity study of doxefazepam administered in the diet to Sprague-Dawley rats.

Groups of 50 male and 50 female Sprague-Dawley rats were given food containing sufficient doxefazepam, a benzodiazepine derivative, to ensure intakes of 0, 3, 10, or 30 mg/kg/day. These dosages respectively correspond to 2, 20, and 60 times the mean daily hypnotic dose level of an adult man. Rats were treated for 104 weeks and then euthanized. An extensive autopsy was performed on those animals that died intercurrently and on euthanized animals. The chronic administration of doxefazepam did not influence the survival of the rats. No treatment-related changes in clinical signs and body weight gains occurred and malignant tumor rates were similar in controls and treated animals. A significant linear trend in the incidence of hepatocellular neoplasms, primarily benign, was observed in the female treated groups. This higher incidence was not associated to a higher occurrence of focal hyperplasia or other preneoplastic lesions in treated rats. The brain, a target organ for the pharmacological activity of doxefazepam, was carefully examined to search for microscopic foci of proliferative cells. A total of 12 and 6 malignant gliomas were observed in male and female rats, respectively; only two were noticed at autopsy. These tumors were mainly of the oligodendroglioma type commonly found in aged rats. Their incidence was slightly higher in treated rats, but results were not of statistical significance. The overall evaluation of the present study indicates that doxefazepam is noncarcinogenic in rats. However, the increase in liver adenomas found here as well as in previous bioassays with similar drugs and the lack of reliable historical data on the incidence of brain tumors in benzodiazepine-treated rodents suggest that additional experimental and epidemiological studies should be undertaken to exhaustively assess the toxic potential of this widely used class of drugs.

[Sphenoidal pneumosinus dilatans: a case report (author's transl)]. / Considerazioni su un caso di pneumosinus dilatans sfenoidale.

Pneumosinus dilatans is an abnormal dilatation of a paranasal cavity containing air only. The case described here can be added to the 51 cases in the literature. Various pathogenetic theories have been proposed: mucocele, intrasinus hypertension, inflammation, endocrine disorder. The authors suggest that this pathological form is the result of overextension of a normal process in the morphogenesis of the sinuses. The symptomatology depends on the location and on the rate of onset of the dilatation.

[The use of glucagon in cholangiography]. / L'uso del glucagone in colangiografia.

Certainty of interpretation can be hindered by spasms of the sphincter of Oddi during cholangiography, since these impair the opaqueness of the image of the distal common duct and reduce the bile flow in the duodenum. Recently, especially in the English-speaking world, glucagon has been used to relax the bile ducts. The authors, following this line of experimentation, report on the use of glucagon in intravenous cholangiographic examination (15 cases), in postoperatory cholangiography (3) and in intra-operatory cholangiography (7), for a total of 25 patients, 13 of whom affected with pathological bile-duct conditions. In each type of examination, after the contrast material had been administered, X-rays were taken in the same position before and three or four minutes after the endovenous injection of glucagon. In every case glucagon revealed its intense hypotoning action, a consistent and rapid effect of short duration, the absence of side effects, the possibility of its use in every type of cholangiographic examination and its effectiveness in controlling the degree of diagnostic uncertainty.

[Angiographic and clinical evaluation of the topical administration of nitrate derivatives in distal obstructive arteriopathies of the legs. Initial experiences]. / Valutazione angiografica e clinica dell'applicazione topica di nitroderivati nelle arteriopatie ostruttive distali degli arti inferiori. Prime esperienze.

The vasodilator effect obtained by the topic use of a nitroglycerin compound (TNG) has been angiographically tested on 11 patients affected by distal arteriopathy of the legs. All patients presented arteriosclerotic vascular lesions; two of them also suffered from diabetic angiopathy. Arteriography of the legs has proved to be a very important tool in the evaluation of the patients' response to the administration of the drug. An hour after 80 mg of TNG had been applied to the skin of the examined leg, arteriography showed a marked dilation, especially of the muscular arteries and the undamaged tracts of the arteries of the legs. Angiographic evaluation of the functional blood supply thus obtained provides prognostic information and helps in the choice of the subsequent therapy. Furthermore, the clinical efficacy of prolonged treatment with this drug has been tested in 10 out of the 11 patients. They all responded with an immediate and persistent hemodynamic improvement, evaluated according to Fontaine's classification.

Methadone vs morphine: comparison of their effect on phagocytic functions.

A comparison of the effects of methadone and morphine on phagocytic physiology was carried out in mice, using a number of tests, to estimate the risk of using methadone in maintenance protocols for opiates addicts. Results indicate that methadone, like morphine, reduces (a) R.E.S. activity and (b) PMN superoxide anion production, while unlike morphine it (a) does not produce haematologic changes, (b) does not exacerbate C. albicans infections, (c) does not inhibit phagocytosis and killing by murine polymorphonuclear leukocytes and macrophages, or by rabbit alveolar macrophages, and (d) does not reduce spleen and liver weight. These results are in strict agreement with those previously found in human subjects receiving controlled administration of morphine or methadone. Compared to morphine methadone therefore appears to have a lower toxic potentiality.