Relationship Between Juncturae Tendinum and Sagittal Bands

The juncturae tendinum and sagittal bands transmit precise forces through the dorsum of the hand. Both structures are integral in the mechanics of normal digital extension and in stabilization of the metacarpophalangeal (MCP) joints. Extensor tendon injury, or rupture/attenuation of sagittal bands and/or juncturae tendinum, may disrupt the kinematic chain and lead to a number of abnormal hand postures and motions. Early treatment of extensor tendon and/or sagittal band injury is dependent upon proper recognition of primary pathology. Proper evaluation and the use of special clinical tests should be implemented to rule out other pathologies. Once diagnosed, treatment may consist of relative motion splinting and standard pain/edema control measures to increase joint motion, tendon excursion, and functional use of the hand.     

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10⁻⁴). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.     

'Atypical pneumonia' due to parakeet sensitivity: bird fancier's lung in a 10-year-old girl

p6trinsic allergic alveolitis is rare in childhood, with most of the cases reported due to exposure to avian precipitins (Stiem et al. 1966; Dinda et al. 1969; Chandra & Everly Jones 1972; El-Hefny et al. 1980). We report a 10-year-old girl with bird fancier's lung, and suggest that environmental antigens should be sought in children presenting with non-resolving chest disease.     

Is Beh?et's disease triggered by childhood infection?

In a comparison of 30 patients with Behçet''s disease and 60 age and sex matched community controls an increased risk of Behçet''s disease was associated with tonsillectomy, a history of cold sores, large sibship size, late birth order, travel to countries with high incidence of the disease, and first sexual intercourse before 16 years of age. These findings are consistent with a triggering of the disease by infection during childhood or adolescence in an immunogenetically predisposed host.     

Augmented Renal Clearance Implies a Need for Increased Amoxicillin-Clavulanic Acid Dosing in Critically Ill Children

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [{"type":"clinical-trial","attrs":{"text":"NCT02456974","term_id":"NCT02456974"}}NCT02456974].)