Adaptive behaviour in Angelman syndrome: its profile and relationship to age

Background Angelman syndrome (AS) is a neurodevelopmental disorder usually caused by an anomaly in the maternally inherited chromosome 15. The main features are severe intellectual disability, speech impairment, ataxia, epilepsy, sleep disorder and a behavioural phenotype that reportedly includes happy disposition, attraction to/fascination with water and hypermotoric behaviour. Method We studied the level of adaptive behaviour and the adaptive behavioural profile in the areas of ‘motor skills’, ‘language and communication’, ‘personal life skills’ and ‘community life skills’ in a group of 25 individuals with genetically confirmed AS, to determine whether there is a specific adaptive behaviour profile. Results and conclusions None of the individuals, whatever their chronological age, had reached a developmental age of 3 years. A specific adaptive behaviour profile was found, with ‘personal life skills’ emerging as relative strengths and ‘social and communication skills’ as weaknesses.     

Mapping brain abnormalities in boys with autism

Children with autism spectrum disorder (ASD) exhibit characteristic cognitive and behavioral differences, but no systematic pattern of neuroanatomical differences has been consistently found. Recent neurodevelopmental models posit an abnormal early surge in subcortical white matter growth in at least some autistic children, perhaps normalizing by adulthood, but other studies report subcortical white matter deficits. To investigate the profile of these alterations in 3D, we mapped brain volumetric differences using a relatively new method, tensor‐based morphometry. 3D T1‐weighted brain MRIs of 24 male children with ASD (age: 9.5 years ± 3.2 SD) and 26 age‐matched healthy controls (age: 10.3 ± 2.4 SD) were fluidly registered to match a common anatomical template. Autistic children had significantly enlarged frontal lobes (by 3.6% on the left and 5.1% on the right), and all other lobes of the brain were enlarged significantly, or at trend level. By analyzing the applied deformations statistically point‐by‐point, we detected significant gray matter volume deficits in bilateral parietal, left temporal and left occipital lobes (P = 0.038, corrected), trend‐level cerebral white matter volume excesses, and volume deficits in the cerebellar vermis, adjacent to volume excesses in other cerebellar regions. This profile of excesses and deficits in adjacent regions may (1) indicate impaired neuronal connectivity, resulting from aberrant myelination and/or an inflammatory process, and (2) help to understand inconsistent findings of regional brain tissue excesses and deficits in autism. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Sickle cell anemia patients have low erythropoietin levels for their degree of anemia

We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.     

Hemorheological aspects of leuko-platelet activation in atheromatous diseases: clinical applications

Atherosclerosis (and its evolution towards thrombotic accidents) is now considered to be an inflammatory disease in which the interaction among endothelium, leukocytes and platelets plays a determining role. However, large scale epidemiological studies only indirectly reveal the leukocyte activation through somewhat simplistic markers, such as elastase or leukocyte counts. Interestingly, these markers seem to be independent predictors of ischemia distal to the atheromatous lesion. This leukocyte activation is usually associated with more classical hemorheological disturbances affecting blood viscosity and fibrinogen which, on multivariate analysis, also appear to be determinants of atheromatous lesions and their ischemic and thrombotic consequences, statistically independent of the "classical risk factors". Leukocyte activation probably plays an important role in these hemorheological disturbances, because it is associated with the production of leukocyte secretory products (proteolytic enzymes, free radicals, cytokines) which can alter the red cells and make them more aggregable and more rigid, and can increase the production of fibrinogen. These interactions remain incompletely understood, as illustrated by the still unclear role of NO which, depending on the experimental conditions, can have antiatherogenic or proatherogenic effects. The production by the leukocyte of substances leading to hyperviscosity is amplified by hypoxia, while the improvement in claudication distance resulting from walking exercise is associated with a joint fall of the "classical" factors of viscosity and of leukocyte activation markers. All this suggests that leukocyte activation and hyperviscosity are closely interdependent phenomena in the course of atheromatous disease and that, despite the complexity of these interactions, relatively simple and reasonably priced biological markers of this process will become available to the clinician.     

A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40–60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday–Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1–2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1–2 h prior to radiotherapy 5 times per week (Monday–Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.     

A boy with complete triploidy and unusually long survival

A boy with complete triploidy and extensive external and internal congenital malformations who survived for almost seven months is presented. He was born after 31 weeks of gestation, was utterly small for gestational age and the delivery was induced because of intrauterine asphyxia. The infant had typical features of the complete triploidy syndrome. He did not develop mentally or motorically even to a normal neonatal level. Banding analysis of chromosomes and HLA-antigen typing of the patient and his parents suggested that the abnormal cell division had occurred during the oogenesis. The boy suffered a fatal Pneumocystis carinii infection, suggesting defective cellular immunity. In the vast majority of previously reported cases of complete triploidy the infant has died either before birth or within the first postnatal hours and except for four patients, all reported patients have died before the age of 2 months. Our patient illustrates the fact that with modern neonatal intensive care, infants with severe malformation syndromes can survive for longer periods than previously, but in the case of patients with the complete triploidy syndrome without developing mentally at all. The ethical problem of artificially prolonged survival in severely handicapped children is discussed.     

Infantile spasms and neuronal heterotopias. A report on six cases

Six infants with infantile spasms are presented, three primarily considered idiopathic and three symptomatic. Autopsy unexpectedly revealed heterotopias, cortical dyslamination, and other brain malformations in all six cases. No history of any etiologic moment during the neuronal migratory period of early gestation was found. It is concluded that wide-spread disturbances of CNS morphology should always be considered in cases of infantile spasms.     

Autologous bone marrow transplantation in the treatment of children and adolescents with advanced malignant tumors

Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m² i.v. and adriamycin 60 mg/m² i.v. on day ?7; cyclophosphamide 45 mg/kg i.v. on days ?6 to ?3), total body irradiation (TBI, 600 rads on day ?1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intraabdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5 +, 5 +, 20 +, 23 +, and 35 + months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.     

Synchronous lung cancer; clinical case of triple lung carcinoma

The case of a 57-year-old man with three synchronous malignancies of the lung (adenocarcinoma, small cell carcinoma, squamous carcinoma in situ) is presented. This is one of the few cases reported in the literature with three different histologic types in the same pulmonary lobe.