Corneal Melting Two Weeks after Pterygium Excision with Topical Mitomycin C: Successfully Treated with Lamellar Keratoplasty and Amnion Membrane Transplantation

Purpose

To report the management of a case of corneal melting two weeks after pterygium excision with intraoperative topical mitomycin C (MMC).

Methods

Case report.

Results

A 57-year-old male was referred to our Department for therapy of rapidly progressive corneal melting two weeks after primary pterygium surgery with MMC (0.2 mg/ml) in September 2009. Initial treatment consisted of topical and systemic immunosuppression along with topical antibiotics. Eight days after presentation, the patient underwent successful lamellar keratoplasty and amnion membrane transplantation. Subconjunctival injection of triamcinolone (40 mg/ml) and topical bevacizumab were used to manage the increased fibrovascular activity around the site of the former pterygium.

Conclusion

Topical use of MMC during pterygium surgery may be related to serious postoperative complications such as progressive inflammatory corneal melting. The etiology may be multifactorial, which is related to MMC-induced inflammation and/or induced apoptosis. A therapeutic option is the described combination of systemic and local anti-inflammatory treatment along with lamellar keratoplasty and amniotic membrane transplantation. Adjunctive therapy may be needed if recurrence occurs.Key words: Mitomycin C, Pterygium, Corneal melting, Amniotic membrane, Lamellar keratoplasty     

Testing for aerobic heterotrophic bacteria allows no prediction of contamination with potentially pathogenic bacteria in the output water of dental chair units

Background: Currently, to our knowledge, quality of output water of dental chair units is not covered by specific regulations in the European Union, and national recommendations are heterogeneous. In Germany, water used in dental chair units must follow drinking water quality. In the United States of America, testing for aerobic heterotrophic bacteria is recommended. The present study was performed to evaluate whether the counts of aerobic heterotrophic bacteria correlate with the presence of potentially pathogenic bacteria such as Legionella spp. or Pseudomonas aeruginosa. Methods: 71 samples were collected from 26 dental chair units with integrated disinfection device and 31 samples from 15 outlets of the water distribution pipework within the department were examined. Samples were tested for aerobic heterotrophic bacteria at 35°C and 22°C using different culture media and for Legionella spp. and for Pseudomonas aeruginosa. Additionally, strains of Legionella pneumophila serogroup 1 were typed with monoclonal antibodies and representative samples of Legionella pneumophila serogroup 1 were typed by sequence based typing.Results: Our results showed a correlation between different agars for aerobic heterotrophic bacteria but no correlation for the count of aerobic heterotrophic bacteria and the presence of Legionella spp. or Pseudomonas aeruginosa.Conclusion: Testing for aerobic heterotrophic bacteria in output water or water distribution pipework within the departments alone is without any value for predicting whether the water is contaminated with potentially pathogenic bacteria like Legionella spp. or Pseudomonas aeruginosa.     

A Sustainable Course in Research Mentoring

In this report, we describe a six‐year experience (2007‐2012) in a single CTSA awardee institution on the development, implementation and evaluation of a hybrid online mentoring curriculum that is applicable to CTSA trainees at various levels (graduate, medical students, and junior faculty) of career training. The curriculum offers convenience, engagement, and financial sustainability. Overall, we found high levels of satisfaction with the curriculum and mentoring experience among both protégés and mentors. Qualitative data showed remarkable consensus of 14 of the 15 domains of mentoring that form the framework of the mentoring curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4) teaching/training, (5) clarity of performance/expectations, (6) sponsorship/sharing power judiciously, (7) demystifying the system (academia), (8) challenging/encouraging risk taking, (9) affirming, (10) providing exposure/visibility, (11) being an intentional role model, (12) protecting, (13) providing feedback, (14) self‐disclosure, and lastly (15) counseling, with the fifteenth domain “counseling” being the most controversial. Quantitative survey data of both mentors and protégés indicated a high degree of overall satisfaction in their mentor‐protégé dyad with 86% (59) of protégés and 86% (55) of mentors responding good or excellent to the “quality of time spent.” Mentors and protégés were most satisfied in the area of research, with 93% (62) of protégés and 96% (57) of mentors finding discussions in research very to somewhat useful for their own career advancement. Along with wide acceptability, this format is a useful option for institutions where face‐to‐face time is limited and education budgets are lean.     

Suppression of hypoxia-inducible factor-1α contributes to the antiangiogenic activity of red propolis polyphenols in human endothelial cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1α (HIF1α) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent manner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1α protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1α protein half-life from ~58 min to 38 min under hypoxic conditions. The reduced HIF1α protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1α. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1α. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1α protein accumulation and signaling.     

DNA Repair Polymorphisms in B-cell Chronic Lymphocytic Leukemia in Sufferers of Chernobyl Nuclear Power Plant Accident

An association between DNA repair gene polymorphisms, environmental factors, and development of some types of cancer has been suggested by several studies. Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the clean-up workers of the Chernobyl Nuclear Power Plant (NPP) accident and it has some specific features. Therefore, we have studied the possible differences in DNA repair gene polymorphisms in CLL patients depending on ionizing radiation (IR) exposure history and their clinical characterictics. Arg399Gln XRCC1, Thr241Met XRCC3, and Lys751Gln XPD polymorphisms were studied in 64 CLL patients, exposed to IR due to the Chernobyl NPP accident, 114 IR-non-exposed CLL patients, and 103 sex- and age-matched IR-exposed controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. All investigated polymorphisms were equally distributed between two groups of CLL patients and IR-exposed controls, except that that there was a significant reduction of the common homozygous Lys/Lys XPD genotype among IR-exposed CLL patients (23.7%) compared with IR-exposed controls (45.6%), OR = 0.37; 95% CI = 0.18-0.75; (P = 0.005). The number of IR-non-exposed CLL patients (37.4%) with the Lys/Lys XPD genotype was also decreased compared to IR-exposed controls, although this difference was not significant (P = 0.223). These preliminary data suggest a possible modifying role of Lys751Gln XPD polymorphism for the development of CLL, expecially in radiation-exposed persons.     

Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to beta thalassaemia

The analysis of polymerase chain reaction (PCR)-amplified beta-globin DNA with allele-specific oligonucleotide (ASO) probes reveals a very heterogeneous spectrum of beta-thalassaemia in the Netherlands. However about 20% of the beta-thalassemia mutations cannot be identified with this approach. The combination of specific amplification of certain regions of the beta-globin gene with denaturing gradient gel electrophoresis (DGGE) allowed us to rapidly localize several of these mutations to specific regions of the gene, which were again amplified and directly sequenced. We believe that the combination of DGGE and the direct sequence determination of PCR amplified genomic DNA represents a valid alternative to the 'ASO probes' approach, especially in countries where a very heterogeneous spectrum of beta-thalassaemia mutations occurs.     

Pubertal and gender-related changes in the sympathoadrenal system in healthy children

A critical amount of body fat is necessary for the initiation of puberty, and leptin, an adipocyte-derived hormone, is necessary for pubertal development. The sympathoadrenal system modulates body fat stores and leptin secretion and interacts with adrenocortical androgen production, suggesting a possible role in sexual maturation. We studied sympathetic nerve and adrenomedullary activity at rest in 80 healthy children (ages, 5-17 yr; 37 boys and 43 girls) in relation to age, pubertal stage, gender, physical activity, body mass index, and serum levels of sex steroids, dehydroepiandrosterone sulfate, cortisol, leptin, and insulin. Plasma concentrations of the adrenomedullary hormone, epinephrine (E), and its metabolite metanephrine (MN), decreased significantly with advancing puberty and were higher in boys than in girls. E and MN correlated significantly and inversely with dehydroepiandrosterone sulfate, estradiol, testosterone, leptin, and insulin. Plasma norepinephrine, which is primarily derived from sympathetic nerve endings, increased significantly with advancing puberty and increasing testosterone levels in boys. Stepwise multiple regression analysis revealed that E was best predicted by pubertal stage and leptin, and MN by estradiol and leptin. Our data suggest that sympathoadrenal hormones may play a role in the complex process of sexual maturation. Further studies are needed to investigate a possible modulatory role of the adrenal medulla in the body weight-related timing of adrenarche and/or gonadarche.     

Lipid levels and their genetic regulation in patients with familial hypercholesterolemia and familial defective apolipoprotein B-100: the MEDPED Slovakia Project

We examined, from a cohort of 165 families, 529 individuals for familial hypercholesterolemia (FH). Utilising clinical criteria for diagnosis, we identified 122 patients (n=41 families) as having FH. With PCR testing, 31 individuals (n=12 families) were found to have familial defective Apo B-100 (FDB). From the cohort, 102 normolipidemic (NL) individuals served as a control group. Patients with FH had the highest levels of total cholesterol (TC), LDL-cholesterol (LDL-C) and apolipoprotein B (Apo B), followed by FDB patients and the normolipidemic relatives had the lowest levels (P<0.0001 for all parameters). We did not find any effect of Apo E genotypes on lipid levels in the NL or FH group. Therefore, other genetic and/or environmental factors may be responsible for the diversity in the clinical expression in these populations.     

Clinical phenotype,biochemical profile,and treatment in 19 patients with arginase 1 deficiency

Background

Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD). This hypothesis-generating study explored clinical phenotypes, metabolic profiles, molecular genetics, and treatment approaches in a cohort of children and adults with ARG1 deficiency to add to our understanding of the underlying pathophysiology.

Methods

Clinical data were retrieved retrospectively from physicians using a questionnaire survey. Plasma aminoacids, guanidinoacetate (GAA), parameters indicating oxidative stress and nitric oxide (NO) synthesis as well as asymmetric dimethylarginine (ADMA) were measured at a single study site.

Results

Nineteen individuals with ARG1 deficiency and 19 matched controls were included in the study. In patients, paraparesis, cognitive impairment, and seizures were significantly associated suggesting a shared underlying pathophysiology. In patients plasma GAA exceeded normal ranges and plasma ADMA was significantly elevated. Compared to controls, nitrate was significantly higher, and the nitrite:nitrate ratio significantly lower in subjects with ARG1 deficiency suggesting an advantage for NO synthesis by inducible NO synthase (iNOS) over endothelial NOS (eNOS). Logistic regression revealed no significant impact of any of the biochemical parameters (including arginine, nitrates, ADMA, GAA, oxidative stress) or protein restriction on long-term outcome.

Conclusion

Three main hypotheses which must be evaluated in a hypothesis driven confirmatory study are delineated from this study: 1) clinical manifestations in ARG1 deficiency are not correlated with arginine, protein intake, ADMA, nitrates or oxidative stress. 2) GAA is elevated and may be a marker or an active part of the pathophysiology of ARG1 deficiency. 3) Perturbations of NO metabolism merit future attention in ARG1 deficiency.