Neurodevelopmental outcomes in children with cerebellar malformations: a systematic review

Cerebellar malformations are increasingly diagnosed in the fetal period. Consequently, their consideration requires stressful and often critical decisions from both clinicians and families. This has resulted in an emergent need to understand better the impact of these early life lesions on child development. We performed a comprehensive literature search of studies describing neurodevelopmental outcomes of cerebellar malformations between January 1997 and December 2007. Overall, the data suggested that children with isolated inferior vermis hypoplasia (IVH) and mega cisterna magna (MCM) have a good developmental outcome, whereas children with molar tooth sign/Joubert syndrome, vermis hypoplasia, pontocerebellar hypoplasia (PCH) type II, and cerebellar agenesis experience moderate to severe global developmental delays. Reports for Dandy−Walker malformation (DWM) were conflicting; however, the presence of a normally lobulated vermis and the absence of associated brain anomalies were associated with a more favourable outcome. Finally, children with isolated cerebellar hypoplasia experienced fewer impairments. Important methodological limitations highlighted include a lack of standardized outcome measure use in 79% of studies and the predominant use of retrospective study designs (85%), with 40% limited to case reports or case-series. In summary, rigorous outcome studies describing the spectrum of disabilities in survivors are urgently needed to accurately delineate the long-term neurodevelopmental consequences of cerebellar malformations.     

Solution conformations of the peptide backbone for DPDPE and its β-MePhe4-substituted analogs

The solution structures of DPDPE, a conformationally restricted pentapeptide with the sequence H-Tyr¹-d -Pen²-Gly³-Phe⁴-d -Pen⁵-OH, and its four β-MePhe⁴-substituted analogs were examined by a combined approach including the NMR measurements in DMSO and water as well as independent energy calculations. It was concluded that several low energy conformers of DPDPE backbone satisfy the NMR data obtained in this study as well as in previous studies by other authors. These possible solution conformers of DPDPE in both DMSO and water share virtually the same type of cyclic backbone structure, with the Gly³ residue in a conformation close to a γ-turn, and the Phe⁴ residue in a conformation close to α-helical torsion angles. They differ in the space arrangements of the flexible Tyr¹ moiety. The solution structures of the β-MePhe⁴-substituted analogs of DPDPE are interesting. For analogs with an S-configuration at the C^α atom in the Phe⁴ residue, the cyclic backbone conformations resemble those of DPDPE itself, whereas for analogs with an R-configuration at the C^α atom, the backbone conformation is somewhat different. This observation is in line with the high biological potencies and selectivities displayed by the former compounds but not by the latter ones. It was noted also that as far as the peptide backbone conformers are concerned, some of the possible DPDPE conformers in water are similar to the previously suggested model for the δ-receptor-bound conformation of DPDPE, becoming virtually identical to this conformation by rotating the side chains of the Tyr¹ and the Phe⁴ residues.     

Prechronic Inhalation Toxicity Studies of 2-Mercaptobenzimidazole (2-MBI)in F344/N Rats

2-Mercaptobenzimidazole (2-MBI), used in rubber processing,is a suspect carcinogen structurally related to ethylene thiourea.The inhalation toxicity of 2-MBI was evaluated in male and femaleF344/N rats exposed 6 hr/day, 5 days/week to respirable aerosolsgenerated by spray atomization of aqueous suspensions of the2-MBI powder and subsequent drying of the resulting aerosols.Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0,50.0, or 100 mg/m³ of 2-MBI produced a dose-related reductionin body weight gains, thyroid follicular cell hyperplasia, adrenalcortex fatty change, and pituitary atrophy. Sub-chronic exposureswere conducted at target concentrations of 0, 3.1, 6.2, 12.5,25.0, and 50.0 mg/m³ of 2-MBI. Rats at 25 mg/m³ displayed hunchedposture, hypoactivity, and reduced body weight gain, with compoundrelated mortality at the highest exposure level. Anemia; increasedSGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN,and cholesterol; and reduced free fatty acid were seen in ratsat 25 mg/m³. Increased thyroid weight and thyroid follicularcell hyperplasia were noted in both sexes at 6.2 mg/m³, withreduced triiodothyronine and thyroxine levels in both sexesat > 12.5 mg/m³. Thyroid follicular cell hyperplasia wasalso seen in rats at 3.1 mg/m³. Thymus weights were significantlyreduced in both sexes at all exposure levels with liver weightincreases at 6.2 mg/m³. Exposure-related histopathologic changesincluded pituitary cytoplasmic vacuolization, adrenal cortexnecrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy,renal mineralization and tubular atrophy, and hypocellularityof the bone marrow.     

Comparison of salbutamol powder with terbutaline aerosol administered with a tube spacer in asthmatic children

ABSTRACT. The bronchodilator effect of 400 μ of salbutamol powder (2 capsules) administered by a rota-haler was compared with that of 500 μg of terbutaline (2 mete red doses) administered as an aerosol via a tube-spacer in a group of ten stable asthmatic children (mean age 12 years). The salbutamol powder produced significantly greater bronchodilatation compared with the terbutaline. Forty-five minutes after the administration of each preparation, nebulised salbutamol was given to determine if further bronchodilatation was possible. Additional bronchodilatation was seen in both groups, the greater additional change being after terbutaline. It is concluded that 400 μg of salbutamol powder was more effective than 500 μg of terbutaline via tube-spacer but following both preparations, nebulised salbutamol produced significant additional bronchodilatation.     

Clinical and psychosocial service needs of children and families affected by human immunodeficiency virus in Europe

Background: Although human immunodeficiency virus (HIV)-infectedchildren have specific service needs, uninfected children bornto HIV-infected mothers are also likely to be profoundly affectedby HIV. However, there has been little systematic documentationof services available for families with HIV infection in Europeor any investigation into service use by families and theirsatisfaction with current provision. Methods: A two-part surveywas carried out: interviews with service-providers in 15 paediatricHIV centres in Europe were carried out to obtain informationon current provision of clinical and psychosocial services.This was followed by an anonymous, self-completed questionnairesurvey of parents and carers of children attending ten of these15 centres. Results: Most (nine out of 15) centres had weeklycase-loads of more than ten HIV-infected and -affected children.Three-quarters (138 out of 182) of the families surveyed includedat least one HIV-infected child. In most (13 out of 15) clinicsa psychosocial professional was routinely available, in additionto paediatricians. Service users reported general satisfactionwith clinic organization, such as medical appointment schedules,continuity of in-and out-patient care and coordination of adultand child appointments. The level of information provided wasconsidered satisfactory by most service users, although parentstended to be less satisfied than alternative carers. Sick parentsand unemployed respondents had the highest level of serviceuse and three-quarters of service users reported unmet serviceneeds. Conclusion: The range of services provided was remarkablysimilar across countries, which may reflect the fact that allcentres were referral centres. However, the challenge of meetingthe outstanding service needs of certain families remains.