Adriamycin-induced histamine release from heart tissue in vitro

 It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells. As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the clinically employed formulation. Received: 18 August 1996 / Accepted: 22 December 1996     

Management of uterine giant myoma

BACKGROUND: Giant myomas of the uterus are uncommon, particularly in developed countries. CASE: This report illustrates a case of a woman with a bilobated giant myoma of the uterus weighed in total 27.7 kg. The patient had an abdominal distension first noted 18 months before and the personal history evidenced difficulties in walking and tiredness. Abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. CONCLUSIONS: The knowledge of the different clinical manifestation of these myomas may allow to face that with adequate perioperative care, in order to assure a carefully and successfully surgery, although sometimes a benign pathology may be not easy to suspect in a first time.     

Die sympathischen Ganglien des Magens bei einigen experimentellen und spontanen Magenkrankheiten

Ohne ZusammenfassungHierzu Tafel V.Die Anregung, Leitung und Redaktion der Arbeit ging von Dr. d'Amato aus, die technische Ausführung von Dr. Macrì.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

The effect of learning to drum on behavior and brain function in autistic adolescents

This current study aimed to investigate the impact of drum training on behavior and brain function in autistic adolescents with no prior drumming experience. Thirty-six autistic adolescents were recruited and randomly assigned to one of two groups. The drum group received individual drum tuition (two lessons per week over an 8-wk period), while the control group did not. All participants attended a testing session before and after the 8-wk period. Each session included a drumming assessment, an MRI scan, and a parent completing questionnaires relating to the participants’ behavioral difficulties. Results showed that improvements in drumming performance were associated with a significant reduction in hyperactivity and inattention difficulties in drummers compared to controls. The fMRI results demonstrated increased functional connectivity in brain areas responsible for inhibitory control, action outcomes monitoring, and self-regulation. In particular, seed-to-voxel analyses revealed an increased functional connectivity in the right inferior frontal gyrus and the right dorsolateral prefrontal cortex. A multivariate pattern analysis demonstrated significant changes in the medial frontal cortex, the left and right paracingulate cortex, the subcallosal cortex, the left frontal pole, the caudate, and the left nucleus accumbens. In conclusion, this study investigates the impact of a drum-based intervention on neural and behavioral outcomes in autistic adolescents. We hope that these findings will inform further research and trials into the potential use of drum-based interventions in benefitting clinical populations with inhibition-related disorders and emotional and behavioral difficulties.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and social interactions as well as a range of restricted, repetitive interests, activities, and behaviors (1). Over recent decades, incidence estimates for ASD have increased (2), with a prevalence of 1 in 59 children in the United States (3) and over 600,000 people in the United Kingdom, which is equivalent to a population prevalence of ∼1% (4, 5). In this context of increased autism prevalence, there is an existing need to develop interventions that offer new insights and perspectives and help address the specifically high demand for services for autistic adolescents and young adults (6). [The term “autistic” is used throughout this paper because of a large percentage of the UK autism community’s preference for the identity-first construction (e.g., “autistic person”) over the person-first phrase (e.g., “person with autism”) (7).] Indeed, autistic young people often face discontinuity in care provision in the transitionary period from child and adolescent services to adult services, just when their care needs are most pressing, making their transition into adulthood particularly difficult (8). In particular, mismatches across services, such as differences in eligibility criteria or age cutoffs, mean that many autistic young adults fall through the care gap after exiting high school (8). Autistic individuals are particularly vulnerable during this period because they often face high unemployment rates, increased levels of comorbid psychiatric diagnoses such as anxiety and depression, and, more broadly, greater reliance on assistance from others when it comes to carrying out adulthood-related daily activities (9–11).A growing body of research suggests that key social domains of the ASD symptomatology may be related to atypical executive functioning (12, 13). Inhibitory control, one of the core executive functions (EFs), corresponds to the ability to delay the onset of behavioral responses, or withhold behaviors that are prepotent but contextually inappropriate (14, 15). It works in concert with other EFs, such as cognitive flexibility and working memory, to exert top-down control on behavioral responses, enable self-regulation, and help navigate social relationships, therefore supporting transition into adulthood and independent living (16, 17). More specifically, it is thought that atypical inhibitory control in autism may underlie significant strengths but may also exacerbate key features of the ASD symptomatology, such as struggling with change and uncertainty, or having difficulty interpreting social cues (18–21). Impaired performance on inhibitory control tasks is frequent in autistic individuals (12, 13, 22, 23). In particular, it has been associated with severe restricted and repetitive behaviors (19, 24, 25), as well as a deficit in proactive response slowing [the ability to slow the initiation of a behavioral response in preparation for stopping during conditions of uncertainty (19)]. At the neuroimaging level, prior studies have revealed atypical recruitment of frontal regions in autistic adolescents (20), and impaired functional connectivity (FC) of the inferior frontal junction, key regions for inhibitory control, in autistic children (26).Autistic individuals often report being preoccupied with certain topics (27) and struggling with anxiety and anger management (28, 29). In a study by Van Hees et al. (30), higher-education autistic students described feeling overwhelmed by the demands placed on them while facing significant difficulties with planning, information processing, time management, organizational skills, and sensory overload. These difficulties may reflect impaired attention and inhibition abilities, complementary processes that allow individuals to pursue the achievement of a particular goal while remaining flexibly responsive to environmental demands (21, 31). A research study on a population-based twin sample of 17,000 children (9 y to 12 y old) concluded that the vast majority of children with ASD traits also exhibit cooccurring attention deficit and hyperactivity disorder (ADHD) traits (32). More specifically, the authors demonstrated that 82% of the boys and 95% of the girls with high ASD traits on all three ASD domains (social impairments, communication impairments, and restricted repetitive behaviors and interests) exhibited difficulties on at least one of the three ADHD domains (attentional difficulties, hyperactivity, and impulsivity). Additionally, they reported that repetitive and restricted behaviors in ASD correlated with ADHD domains, particularly with impulsivity and attentional difficulties. This is in line with a previous twin study in adults, which reported the highest phenotypic and genetic overlap between ADHD traits and “nonsocial” autistic-like traits such as attention switching difficulties (33).Music has long been known to promote cognitive and emotional wellbeing in both clinical and healthy populations (34, 35). Rhythm-based musical training, in particular, has been shown to enhance higher-order cognition and motor control (31). There is growing evidence that activities designed to improve beat synchronization skills may provide an effective approach to developing neurological processes that underpin self-regulation and EF skills (36). Indeed, EF deficits have been linked with poor rhythm perception in children (37) and poor sensorimotor synchronization in young adults (38). Using the Integrated Visual and Auditory Plus Continuous Performance Test (39), Slater et al. (31) highlighted that drumming practice is associated with better scores in inhibitory control and selective attention in adult percussionists compared to nonmusicians.More specifically, learning to drum requires error monitoring and temporal accuracy and therefore both attentional and inhibitory control (31, 40). In a recent study, Lowry et al. (40) used a mixed-methods analysis to investigate behavioral changes in children with emotional and behavioral difficulties, after learning to drum. Following drum training, the participants displayed enhanced attentional focus and reduced hyperactivity and peer problems (40). These results concur with Draper et al.’s (41) recent findings showing that drumming improves motor control and attentional focus and reduces emotional and peer problems in autistic children. It is important to note that motor control is particularly relevant in the context of ASD. Indeed, recent studies have consistently demonstrated motor impairments across the autism spectrum (42, 43), including gross and fine motor difficulties (44, 45) and delays with motor planning (46). Sokhadze et al. (47) showed that ∼80% of autistic individuals also present with clumsiness or motor dyspraxia, which can manifest as having difficulty with motor coordination as well as concentration, planning, and organization. These difficulties may impact the individual’s ability to carry out daily activities, which, in turn, can lead to rejection from peers and social isolation (48). Similarly, motor impairments in balance, motor accuracy, and object manipulation scores have been reported to be predictive of social dysfunction in young autistic boys (49). In this context, learning to drum could be regarded as particularly beneficial because it involves not only musicality but also the development of multimodal skills such as body coordination, sensorimotor integration, and cardiovascular exercise processes (50). Additionally, it is appealing and accessible to everyone regardless of age, gender, ethnicity, or musical background (51, 52).In our proof-of-concept study, Amad et al. (53) showed that the brain is capable of neuroplastic modifications through drum-based practice in neurotypical adolescents. In particular, changes in FC were observed post drum training in brain regions known to exhibit atypical functioning in autism, such as areas associated with motor skills and the mirror neuron system.In the present study, we investigated the impact of drum training on brain function in 36 autistic adolescents who were split into two age- and gender-matched groups: a drum group (n = 19), who were evaluated before and after learning to drum, and a control group (n = 17), who were also evaluated longitudinally but with no intervention. We explored behavioral outcomes related to drum practice in this clinical population and examined their association with changes in FC between the two groups (i.e., drum group vs. control group) over time (i.e., before vs. after drum training).We hypothesized that drumming performance would improve in the drum group over time, while no improvement would be observed in the control group. Furthermore, we hypothesized that changes in hyperactivity, attentional difficulties, problem behaviors, and repetitive and restricted behaviors would be observed in the drum group. We also hypothesized that cooccurring changes in FC in brain areas responsible for attentional focus and inhibitory control would be identified following drum training.