External beam irradiation in the palliation of bone metastases: a practice analysis among Sicilian Departments of Radiation Oncology

BACKGROUND: In the treatment of bone metastases, the choice of radiation fractionation, total radiation dose, delivery technique, and imaging studies before treatment varies among radiation oncologists. Surveys on this issue, using case scenarios, have been published by groups from Europe, North America, and Australia-New Zealand. Our objective was to analyze retrospectively the "real" practice in nine radiotherapy centers located in Sicily. METHOD: A questionnaire including 17 items was distributed to 30 practicing radiation oncologists working in seven departments of four Sicilian cities (Messina, Catania, Ragusa and Palermo) during a meeting of the Sicilian Division of the Associazione Italiana Radioterapia Oncologica (AIRO). Participants were asked to answer the questions using a card for every patient treated with external beam irradiation from 1 January to 31 December, 2000. RESULTS: Six centers returned the questionnaires; 332 cards were valuable for a total of 5644 responses. All six responding departments used linear accelerators for treatment delivery. The most common dose fractionation was 30 Gy in 10 fractions and the most common technique used was opposed parallel local fields. Before the start of irradiation a bone scan was performed in 325 of the 332 (98%) patients treated and CT and/or MRI was performed in 320 (96%); surprisingly, standard roentgenograms were used in only 142 of 332 patients (42.8%). CONCLUSION: The "real" radiation practice for bone metastases in the region of Sicily confirms the results of the previously reported international surveys: there is a clear preference for fractionated treatment and local field therapy. The results of randomized studies, which demonstrated both the efficacy and the feasibility of a single 6-8 Gy fraction in the palliation of bone metastases, have little or no impact on the pattern of practice.     

Developmental and tissue-specific regulation of a novel dysferlin isoform

Dysferlin plays an essential role in the muscle repair machinery, and its deficiency is associated with limb-girdle muscular dystrophy type 2B and with two different distal myopathies (Miyoshi myopathy and distal anterior compartment myopathy). Our aims were to characterize the pattern of dysferlin expression during myogenic cell differentiation and to assess possible differentially spliced isoforms of the DYSF gene. Human primary myogenic cells express a splice variant of dysferlin mRNA lacking exon 17 (Delta17), together with full-length dysferlin mRNA. Real-time polymerase chain reaction analysis of human myoblasts, myotubes, and normal skeletal muscle showed that Delta17 expression inversely correlates with muscle differentiation. Indeed, Delta17 is progressively replaced by the wild type as myoblast fusion proceeds, and it disappears in adult skeletal muscle. Conversely, Delta17 is the predominant dysferlin variant in mature peripheral nerve. Our findings suggest that the two proteins play different roles in myogenic cell differentiation and that dysferlin function in peripheral nerve might be accomplished by this novel isoform.     

Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2

Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na+,K+-ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.     

Cerebral microembolism during transcatheter closure of patent foramen ovale

BACKGROUND: Although transcatheter closure of patent foramen ovale (PFO) and atrial septal defect (ASD) has become a commonly performed intervention, the incidence of cerebral embolism with or without neurological deficits during such procedures has not been studied. METHODS: We monitored the middle cerebral artery in two different depths (48 mm and 53 mm) by continuous transcranial Doppler ultrasound during transcatheter PFO closure in 35 consecutive patients (F/M 20/15, mean age 47 +/- 11 years) and during ASD closure in 8 patients (F/M 7/1, mean age 45 +/- 5 years). All automatically detected high intensity transient signals (HITS) were manually reviewed to eliminate artifacts. RESULTS: HITS were detected in 33 of 35 patients (96%) with a median rate of 8 (interquartile range 4-19, range 2-29) HITS. The highest rates were observed when the septum was crossed with the guide wire (median 2; IQR 0-12; range 0-25) and when the left atrial disc was deployed (median 2; IQR 1-4; range 0-13). Despite this high rate of cerebral microembolism no clinically apparent neurological or neuropsychological deficit was observed. CONCLUSIONS: Silent cerebral embolism frequently occurs during transcatheter PFO and ASD closure. The peak of HITS at the time of crossing the septum with the guide wire may support the hypothesis that cerebral emboli in patients with PFO may originate from the septum itself. This may represent an alternative mechanism to the generally assumed paradoxical embolism.     

Altered vulnerability to kainate excitotoxicity of transgenic-Cu/Zn SOD1 neurones

The neurotoxicity of the AMPA/kainate receptor agonist kainate was investigated in motor and cortical neurones from mice over-expressing the wild-type and G93A mutant form of Cu/Zn superoxide dismutase (SOD1) human gene, a mouse model of familial amyotrophic lateral sclerosis. G93A mutant motor neurones were more vulnerable and wild-type SOD1 motor neurones were more resistant to kainate toxicity than were controls. Voltage-gated Na channels blockage prevented G93A mutant SOD1 motor neurone death. Cortical cultures exhibited fewer differences in their vulnerability to kainate toxicity. These results demonstrate that SOD1 over-expression selectively affects the sensitivity to kainate excitotoxicity of motor neurones but not neocortical neurones, and that wild-type SOD1 expression increases the resistance to excitotoxicity of motor neurones.     

Syncope of psychiatric origin

Abstract.Background: A well-defined relationship between transient loss of consciousness and a psychiatric disorder has not yet been established.Review summary: In the past, psychiatric origin of syncope was considered to be uncommon, occurring only in 1–7% of patients with syncope. Recently, a much higher incidence ranging from 20 % to 81 % has been reported. One main difficulty may be an incorrect approach to the problem. Authors generally defined syncope as every loss of consciousness without regard to the specific pathophysiology of the symptom. Moreover, identification of psychiatric origin of transient unconsciousness may be very difficult. Some clinical features can suggest the diagnosis; none of them, however, is an identification mark. Thus, in most cases, the diagnosis may be certain only when direct observation of the clinical event occurs. A transient loss of consciousness may be related to a psychiatric disorder when the symptom ensues in the presence of normal values of both blood pressure and heart rate. The phenomenon resembles syncope and has been defined as pseudosyncope. Unfortunately, direct observation of a spontaneous event is very uncommon. Recently, few cases of pseudosyncope induced by Tilting test (HUTT) have been reported. In these patients, HUTT revealed a previously unknown psychiatric disorder. In our experience, pseudosyncope represented an uncommon HUTT outcome in all patients referring for unexplained syncope; in selected patients, however, HUTT may be useful in the early identification of psychiatric syncope.Conclusions: Prospective researches are needed to assess HUTT utility in evaluating patients whose clinical features suggest psychiatric origin of transient loss of consciousness.     

Learning modulation by endogenous hippocampal IL-1: blockade of endogenous IL-1 facilitates memory formation

The interleukin-1 (IL-1) cytokine family (IL-1alpha, IL-beta, and the IL-1 receptor antagonist) is involved in immune and inflammatory responses both in the brain and in the periphery. Recently, it has also been shown to influence behavior and memory consolidation. However, within the experimental systems studied, it has remained unclear whether the role of IL-1beta is associated solely with a pathophysiological process or whether it is a neuromodulator in normal adult brain. To evaluate the involvement of the nonpathological endogenous IL-1 system in learning, we studied the expression of IL-1alpha, IL-1beta, and IL-1ra during memory consolidation. We observed a learning-specific hippocampal IL-1alpha mRNA induction, but not that of IL-1beta or IL-1ra mRNAs, after inhibitory avoidance training. Moreover, when IL-1 receptor activity was inhibited using an adenoviral vector that expresses the IL-1 receptor antagonist (IL-1ra) in the hippocampus, both short-term and long-term memory retention scores were facilitated. In contrast, endogenous hippocampal IL-1 played no role in the habituation to a novel environment. These results demonstrate that endogenous hippocampal IL-1 specifically modulates a fear-motivated learning task, and suggest that IL-1alpha activity in the CNS is part of the hippocampal memory processing.     

Defective spatial imagery with pure Gerstmann's syndrome

Gerstmann's syndrome comprises finger agnosia, peripheral agraphia, anarithmetia, and right-left confusion. We here report a single-case study of an 85-year-old ambidextrous man who exhibited pure Gerstmann's syndrome (i.e., without aphasia) 10 weeks after a stroke involving the angular gyrus in the left parietal lobe. We hypothesize that, in this case, the main cognitive denominator of Gerstmann's tetrad was a severe dysfunction in mental rotation and translation. This report provides further evidence for the spatial nature of Gerstmann's syndrome.