Studies on pharmacokinetic mechanism of phenytoin resistance in refractory epilepsy

P-glycoprotein (P-gp) is a drug efflux pump in many organs, including the intestine and liver. Two single nucleotide polymorphisms (SNPs) of P‐gp gene, 2677G>T and 3435C>T, were reported to influence function and expression of P‐gp and have the controversial effects on drug disposition. Phenytoin is one substrate of P-gp. Persistent low phenytoin levels in plasma and P-gp overexpression in brain in several refractory epilepsy patients were reported. P‐gp polymorphisms may also affect phenytoin efficacy by altering its bioavailability (F). Because two P‐gp SNPs, 2677G>T and 3435C>T, may affect P‐gp expression in tissue, we examined phenytoin disposition in patients of different P-gp haplotypes, G/G2677C/C3435 and T/T2677T/T3435. We found that the mean absolute F of phenytoin in T/T2677T/T3435 subjects (91%) is slightly higher than in G/G2677C/C3435 subjects (82%). There was no difference in the maximum concentration (C_max) and the area under the serum concentration–time curve of phenytoin administered orally between two genotypic groups. However, the time of maximum concentration was higher in T/T2677T/T3435 subjects (10 h) than in G/G2677C/C3435 subjects (6 h). The study ruled out the possibility that genetic polymorphisms of P-gp may affect phenytoin efficacy through the decreased absorption or the increased elimination. P-gp SNPs could affect phenytoin efficacy in refractory epilepsy patients probably because of central nervous system.     

Impact of fibrin glue versus suture closure on double-headed pterygia in Asian eyes – a 7-year study in a tertiary institution

BackgroundTo compare the recurrence rate and outcomes of double-headed pterygia using fibrin glue versus suture closure of conjunctival autograft.MethodsAll patients with double-headed pterygia who underwent pterygia excision with conjunctival autograft from January 2012 to January 2019 in the National University Hospital of Singapore were included. Patients were divided into 2 groups depending on whether fibrin glue or sutures were used to secure the conjunctival autograft in place. All patients had a minimum of 6 months follow-up.ResultsA total (26 patients) of 22 eyes had fibrin glue, while eight eyes underwent suture closure of their conjunctival autograft. Fibrin glue group had 4.5% recurrence rate, while suture group had 37.5% recurrence rate (p = .021). There is statistically significant improvement for overall visual acuity (p = .009) and cylinder (p = .002). There is also statistically significant improvement for visual acuity in the glue group (p = .026), but not in the suture group. Fibrin glue group had a shorter operation duration time compared to suture group (p < .001).There were no cases of graft dislocation, contraction or limbal stem cell deficiency.ConclusionsLow recurrence rates and good postoperative visual outcomes can be achieved with the split conjunctival autograft technique. Our study suggests that fibrin glue has an additional benefit over the use of sutures in the management of these complex cases.     

Eruptive poromatosis in a patient with breast cancer

Poromas are a group of benign growths of poroid differentiation derived from cells of the terminal sweat duct and connected to the epidermis, normally presenting as solitary papules, plaques or nodules. Rarely they can be eruptive in nature and as such are described as poromatosis. We report an unusual case of widespread poromatosis occurring in a woman with metastatic breast cancer who had recently completed chemo‐radiotherapy.