Finger pulp reconstruction with thenar flap: Aesthetic and functional outcome

Purpose: Fingertip injuries are common in industrial production activities as well as in domestic work. Loss of pulp hampers daily life activities. Functional and aesthetic aspects are important in fingertip reconstruction. The bone is usually exposed along with soft tissue loss. Therefore to reconstruct the pulp flap with adequate bulk is required. Methods: We reported a case series of 12 patients with the injury over the volar aspect of distal phalanx of the index or middle finger. In all cases, laterally based thenar flap was chosen. The flap donor site was closed primarily in most of cases, while 4 patients required skin graft. The flap was detached between 2-3 weeks. Functional assessment was done using static and dynamic 2-point discrimination and range of motion at each joint. The aesthetic outcome was assessed through questionnaire. The results were analyzed using the unpaired t-test (SPSS version 21). Results: Partial necrosis occurred in 2 cases while rest of flaps survived successfully. Static 2-point discrimination ranged from 6e10 mm, mean 8.6 mm; and dynamic 2-point discrimination ranged from 8-10 mm, mean 8.9 mm. The mean satisfaction score was (4.0 ± 0.55). Conclusion: Thenar flap is a good choice for reconstruction of the finger pulp as it provides the bulk with good functional and aesthetic outcome.     

Development of a Method That Eliminates False-Positive Results due to Nerve Growth Factor Interference in the Assessment of Fulranumab Immunogenicity

Fulranumab, a human IgG2 monoclonal antibody that neutralizes nerve growth factor (NGF), is currently in development for the treatment of pain. Our initial immunogenicity test method was found to be prone to NGF interference, leading to a high apparent incidence of anti-drug antibody (ADA) in phase 1 studies. The ADA immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL) format with biotin and ruthenium-labeled fulranumab bound together (“bridged”) by ADA in test samples for detection. In this assay, NGF produced a false-positive signal due to its ability to bridge fulranumab molecules. Thus, we developed a specificity assay to eliminate the NGF false-positive results. We encountered the challenge of eliminating drug interference as well as drug target interference, and discovered that the acid-dissociation-based pretreatment of samples used for mitigating drug interference dramatically increased drug target interference. Several strategies were investigated to eliminate the NGF interference; yet only one strategy specifically removed NGF and produced true fulranumab-specific ADA results by using competitive inhibition with fulranumab and utilizing an alternative NGF binding antibody to eliminate NGF interference. Using this new method, we confirmed that the high apparent anti-fulranumab antibody incidence (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released during the acid-dissociation step of the ADA testing method. We conclude that our revised method accurately identifies anti-fulranumab antibodies by incorporating steps to eliminate fulranumab and NGF interference. We advise that acid-dissociation pretreatment must not be universally applied to improve ADA assays without investigating its bioanalytical risks versus benefits.     

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety,In Vitro Stability,Ocular Pharmacokinetic Modeling,and Biodistribution

Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [³H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous > retina > sclera/choroid > aqueous humor > cornea > lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [³H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9563-1) contains supplementary material, which is available to authorized users.Key words: age-related macular degeneration (AMD), NA3 glycan, pharmacokinetics, safety     

Unusual presentation of Sturge-Weber syndrome: Progressive megalencephaly with bilateral cutaneous and cortical involvement

The Sturge Weber syndrome is characterized by developmental delay, seizures in infancy, unilateral cutaneous lesions with ipsilateral leptomeningeal enhancement. We report an unusual presentation of Sturge Weber syndrome with bilateral port wine nevus on the trunk and face along with bilateral cortical involvement in a developmentally normal child with progressive megalencephaly.