Acceleration of ALA-induced PpIX fluorescence development in the oral mucosa

BACKGROUND AND OBJECTIVES: The development of 5-aminolevulinic acid (ALA)-induced tissue fluorescence is optimal 2-4 hours after ALA application. Goal of this work was to develop a means of accelerating oral topical ALA-induced tissue fluorescence. STUDY DESIGN/MATERIALS AND METHODS: In 300 hamsters, DMBA (9,10 dimethyl-1,2-benzanthracene) cheek pouch carcinogenesis produced dysplasia in 3-5 weeks. Topical application of 20% ALA in Eucerin was followed by localized ultrasound treatment (1, 3.3 MHz) in 150 animals. In 75 animals, ALA was applied in an Oral Pluronic Lecithin Organogel (OPLO-an absorption enhancer) vehicle. Seventy-five animals received only topical ALA in Eucerin. Hamsters were sacrificed and cryosections underwent fluorescence measurements, histological evaluation, 20-180 minutes after ALA application. One-way ANOVA detected independent effects of pathology on laser-induced fluorescence (LIF). Two-way ANOVA tested for independent effect of pathology and of OPLO, ultrasound, and interaction effects. RESULTS: Ultrasound significantly (P < 0.05) accelerated tissue fluorescence development. CONCLUSIONS: Low-frequency ultrasound can accelerate ALA-induced fluorescence development.     

Sclerosing therapy for orbital lymphangioma using sodium tetradecyl sulfate

PURPOSE: To describe the results of intralesional injection of the sclerosing agent sodium tetradecyl sulfate in patients with orbital lymphangioma. METHODS: Four young patients with a history of orbital lymphangioma were treated on one or more occasions with percutaneous puncture and injection of sodium tetradecyl sulfate under computed tomography guidance. Resolution of the signs and symptoms, complications resulting from surgery, and recurrence of bleeding were studied. RESULTS: Three patients with a long-standing history of unilateral proptosis and one patient with progressive unilateral visual loss from multiple recurrent orbital hemorrhages were studied. Treatment ranged from one to three sodium tetradecyl sulfate injections. All patients showed improvement of their signs and symptoms after treatment. A decrease in the size of lesions was demonstrated by orbital imaging. Visual acuity and intraocular pressure remained unchanged. Complications included transient postoperative localized inflammation in all cases and transient ophthalmoparesis in one patient. Follow-up time ranged between 15 and 36 months, during which no recurrence of bleeding was observed. CONCLUSIONS: Our study suggests that intralesional injection of sodium tetradecyl sulfate under computed tomography guidance is an effective treatment for patients with orbital lymphangioma and is not associated with vision-threatening complications.     

Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia

Background Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.Methods Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.Results We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.Conclusion Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.Subject terms: Genetics research, Cancer genomics, Chronic lymphocytic leukaemia, DNA methylation, Epigenomics     

Evidence suggesting a genetic contribution to kidney stone in northeastern Thai population

Genetic factor may play a role in the pathogenesis of kidney stone that is found in the northeastern (NE) Thai population. Herein, we report initial evidence suggesting genetic contribution to the disease in this population. We examined 1,034 subjects including 135 patients with kidney stone, 551 family members, and 348 villagers by radiography of kidney–ureter–bladder (KUB) and other methods, and also analyzed stones removed by surgical operations. One hundred and sixteen of 551 family members (21.05%) and 23 of the 348 villagers (6.61%) were affected with kidney stone. The relative risk (λ_R) of the disease among family members was 3.18. Calcium stones (whewellite, dahllite, and weddellite) were observed in about 88% of stones analyzed. Our data indicate familial aggregation of kidney stone in this population supporting that genetic factor should play some role in its pathogenesis. Genetic and genomic studies will be conducted to identify the genes associated with the disease.     

Trigeminal fistula treated by combined transvenous and transarterial embolisation

Summary  Trigeminal cavernous fistulae are rare, compared to other types of carotid-cavernous fistulae with only about 17 examples previously reported in English literature. The aetiology can be either post-traumatic or spontaneous, and in the latter group either due to a ruptured trigeminal aneurysm or postulated intrinsic weakness of the artery itself. The treatment goal is to close the fistula while preserving the parent artery and this can be done either by surgical or endovascular methods. We present a 35-year-old woman with a spontaneous trigeminal fistula treated by combined trans-venous and trans-arterial embolisation. Correspondence: S. Geibprasert M.D., Department of Radiology, Ramathibodi Hospital, Mahidol University Pharam 6 Rd, Rachatewi, Bangkok, Thailand.     

Discriminatory powers of molecular typing techniques for methicillin-resistant Staphylococcus aureus in a university hospital, Thailand

Discriminatory powers of various molecular techniques were evaluated for typing of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Siriraj Hospital, Bangkok, Thailand. Thirty MRSA isolates were randomly selected in this study. They were characterized by pulsed-field gel electrophoresis, Clal-mecA and Clal-Tn554 polymorphisms, ribotyping, and PCR-based methods including SCCmec typing, spa and coa gene polymorphism, and repeat units in hypervariable region downstream of mecA. Individual molecular typing technique distinguished those MRSA isolates into 2 to 5 types. Eleven genetic backgrounds of MRSA isolates were elucidated by combination of typing methods with trimethoprim/sulfamethoxazole (TMP/SXT) susceptibility. Combination of all typing methods including TMP/SXT susceptibility yielded a discriminatory index of 0.94. Combination of PCR-based methods and TMP/SXT susceptibility, with the discriminatory index of 0.89, is a practical typing approach suitable for rapid epidemiological investigation of MRSA isolates in a hospital setting.