A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novo change in the father, and of grandpaternal origin. PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycystic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder.      

A Randomized, Multicenter Study of the Safety and Efficacy of Dermicol-P35 and Non–Animal-Stabilized Hyaluronic Acid Gel for the Correction of Nasolabial Folds

BACKGROUND Non–animal-stabilized hyaluronic acid (NASHA) offers longer-lasting cosmetic improvement and reduced risk of hypersensitivity and requires less injection volume than bovine collagen–derived dermal fillers. Porcine collagen–derived Dermicol-P35 has low immunogenicity and has the potential to provide durability at least equivalent to that of NASHA.
OBJECTIVE The objective was to evaluate the efficacy and safety of Dermicol-P35 and NASHA for correction of nasolabial folds (NLFs).
METHODS AND MATERIALS A total of 149 subjects with moderate NLFs were randomized to receive Dermicol-P35 and NASHA on contralateral sides of the face. If needed, subjects could receive a repeat injection 2 weeks later to obtain an optimal cosmetic result (OCR).
RESULTS Significant ( p <.001) improvement in the Modified Fitzpatrick Wrinkle Scale scores relative to screening was observed after treatment with Dermicol-P35 and NASHA. Relative to the OCR visit, mean scores increased ( p <.001) over time, but there were no significant differences between treatments (+0.39 and +0.37 at 6 months; p =.626). Greater proportions of subjects experienced swelling, bruising, and pain at the NASHA site. Several subjects had more induration at the Dermicol-P35 site. There was no evidence of any adverse immunologic effect.
CONCLUSION The effectiveness of Dermicol-P35 is maintained for at least 6 months and is equivalent to NASHA for the correction of NLFs.     

Toward standardization of care: The feeding readiness assessment after congenital cardiac surgery

Background

Feeding practices after neonatal and congenital heart surgery are complicated and variable, which may be associated with prolonged hospitalization length of stay (LOS). Systematic assessment of feeding skills after cardiac surgery may earlier identify those likely to have protracted feeding difficulties, which may promote standardization of care.

Methods

Neonates and infants ≤3 months old admitted for their first cardiac surgery were retrospectively identified during a 1‐year period at a single center. A systematic feeding readiness assessment (FRA) was utilized to score infant feeding skills. FRA scores were assigned immediately prior to surgery and 1, 2, and 3 weeks after surgery. FRA scores were analyzed individually and in combination as predictors of gastrostomy tube (GT) placement prior to hospital discharge by logistic regression.

Results

Eighty‐six patients met inclusion criteria and 69 patients had complete data to be included in the final model. The mean age of admit was five days and 51% were male. Forty‐six percent had single ventricle physiology. Twenty‐nine (42%) underwent GT placement. The model containing both immediate presurgical and 1‐week postoperative FRA scores was of highest utility in predicting discharge with GT (intercept odds = 10.9, P = .0002; sensitivity 69%, specificity 93%, AUC 0.913). The false positive rate was 7.5%.

Conclusions

In this analysis, systematic and standardized measurements of feeding readiness employed immediately before and one week after congenital cardiac surgery predicted need for GT placement prior to hospital discharge. The FRA score may be used to risk stratify patients based on likelihood of prolonged feeding difficulties, which may further improve standardization of care.     

Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review

Aims. In recent years, many different DNA mutations underlying the development of refractory epilepsy have been discovered. However, genetic diagnostics are still not routinely performed during presurgical evaluation and reports on epilepsy surgery outcome for patients with genetic refractory epilepsy are limited. We aimed to create an overview of the literature on seizure outcome following epilepsy surgery in patients with different genetic causes of refractory epilepsy. Methods. We systematically searched PubMed and Embase prior to January 2017 and included studies describing treatment outcome following epilepsy surgery in patients with genetic causes of epilepsy. We excluded studies in which patients were described with epilepsy due to Tuberous Sclerosis Complex or Sturge‐Weber syndrome (since this extensive body of research has recently been described elsewhere) and articles in which surgery was aimed to be palliative. Results. We identified 24 eligible articles, comprising a total of 82 patients who had undergone surgery for (mainly childhood‐onset) refractory epilepsy due to 15 different underlying genetic causes. The success rate of surgery varied widely across these different genetic causes. Surgery was almost never effective in patients with epilepsy due to mutations in genes involved in channel function and synaptic transmission, whereas surgery was significantly more successful regarding seizure control in patients with epilepsy due to mutations in the mTOR pathway. Patients with a lesion on MRI tended to have higher seizure freedom rates than those who were MRI‐negative. Conclusion. Although the evidence is still scarce, this systematic review suggests that studying genetic variations in patients with refractory epilepsy could help guide the selection of surgical candidates.     

Spinal abnormalities in pediatric patients: MR imaging findings compared with clinical, myelographic, and surgical findings

Eighty-one pediatric patients with a variety of spinal disorders, including suspected dysrhaphism, scoliosis, neoplasia, and neurofibromatosis, underwent magnetic resonance (MR) imaging. The results were retrospectively compared with those of myelography followed by computed tomography (CT) and surgery. In patients with dysrhaphism, most abnormalities, including hydromyelia, inclusion tumors, and sites of cord tether, were demonstrated with MR imaging. Diastematomyelia and small hydromyelic cavities were indistinguishable on routine coronal and sagittal T1-weighted images; axial images with T2 weighting were optimal for this differentiation. MR imaging did not enable direct visualization of a thickened filum or evaluation of tethering with a thin, dorsally positioned neural placode. Congenital or severe scoliosis required lengthy studies with multiple planes of imaging or myelography and CT. Milder curvatures were readily evaluated with MR imaging, and neoplastic lesions, with the exception of intrathecal tumor seeding, were adequately defined.     

Molecular cloning of the cDNA for human erythrocyte beta-spectrin

Overlapping cDNA clones, totaling 3.3 kilobases (kb) in length, which encode over 50% of the human erythrocyte beta-spectrin subunit, were isolated by antibody screening of a lambda gt11 expression library constructed from human fetal liver mRNA. The amino acid sequence of the C-terminus of beta-spectrin was derived. The size of beta-spectrin mRNA in human erythroleukemia cells was found to be 7.5 kb. Erythrocyte beta- spectrin is encoded by a gene located on human chromosome 14, as determined by cDNA hybridization to human X mouse somatic cell hybrids.