Laser in situ keratomileusis to correct post-keratoplasty astigmatism; 1-step versus 2-step procedure

PURPOSE: To investigate the correction of post-penetrating keratoplasty (PKP) astigmatism using laser in situ keratomileusis (LASIK). Visual and refractive outcomes were evaluated after LASIK was performed in 1 step (lamellar cut and ablation in 1 procedure) or 2 steps (lamellar cut then ablation in 2 successive procedures). SETTING: Department of Cornea and Refractive Surgery, Vissum-Instituto Oftalmológico de Alicante, University of Miguel Hernández, Alicante, Spain. METHODS: In this prospective observational study, 22 consecutive eyes were divided into 2 groups depending on the LASIK procedure performed to correct post-PKP astigmatism. Group 1 (1-step LASIK) included 11 eyes and Group 2 (2-step LASIK), 11 eyes. The patients were followed for 6 months. RESULTS: A statistically significant improvement was obtained in Group 2 with a mean vector analysis result of the cylinder of -4.37 diopters (D) +/- 1.79 (SD) (P = .018). In Group 1, the mean astigmatism correction was 2.38 +/- 1.71 D. The number of reoperations and residual refractive defects were significantly better in Group 2. CONCLUSION: The 2-step technique improved the accuracy of excimer laser correction of post-PKP astigmatism.     

Generating long‐lived CD8+ T‐cell memory: Insights from epigenetic programs

T‐cell‐based immunological memory has the potential to provide the host with life‐long protection against pathogen reexposure and thus offers tremendous promise for the design of vaccines targeting chronic infections or cancer. In order to exploit this potential in the design of new vaccines, it is necessary to understand how and when memory T cells acquire their poised effector potential, and moreover, how they maintain these properties during homeostatic proliferation. To gain insight into the persistent nature of memory T‐cell functions, investigators have turned their attention to epigenetic mechanisms. Recent efforts have revealed that many of the properties acquired among memory T cells are coupled to stable changes in DNA methylation and histone modifications. Furthermore, it has recently been reported that the delineating features among memory T cells subsets are also linked to distinct epigenetic events, such as permissive and repressive histone modifications and DNA methylation programs, providing exciting new hypotheses regarding their cellular ancestry. Here, we review recent studies focused on epigenetic programs acquired during effector and memory T‐cell differentiation and discuss how these data may shed new light on the developmental path for generating long‐lived CD8⁺ T‐cell memory.     

Outcomes of research biopsies in phase I clinical trials: the MD anderson cancer center experience

Background.

Research biopsies are crucial for exploring the impact of novel agents on putative targets. The current study assesses the safety and success rate associated with performing such biopsies.

Methods.

We reviewed the medical records of 155 consecutive patients who had one or more research biopsies as part of a phase I trial from September 2004 to October 2009.

Results.

Of 281 research biopsies performed, 118 were paired before and after treatment biopsies (total = 236 biopsies). The most common sites of biopsy were superficial lymph node (19.9%), followed by liver (16.4%), and then soft tissue (15.7%). Ultrasound-guided biopsies were the most frequent type (53.7%). Among 142 patients who consented for mandatory biopsy, 86.6% had the biopsy performed, compared with 4.4% of 911 patients offered a biopsy on an optional basis (p < .0001). Biopsy was obtained most frequently on industry-sponsored trials; lack of funding on nonindustry trials was the most common reason that biopsies were not obtained. Of 281 single biopsies, only 4 (1.4%) had complications: pneumothorax requiring chest tube placement (n = 2), infection requiring admission (n = 1), and arrhythmia with hypotension (n = 1). All but one biopsy was successful in obtaining tissue. No deaths were attributable to biopsy.

Conclusions.

Our experience demonstrates that research biopsies in early phase clinical trials are safe (1.4% risk of serious complications), and a higher percentage of patients underwent mandatory biopsies (86.6%) compared with that of the patients with optional biopsies (4.4%).     

Association of Obestatin, Ghrelin, and Inflammatory Cytokines in Obese Patients with Non-alcoholic Fatty Liver Disease

Background

Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.

Methods

We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory data as well as frozen serum samples from the time of liver biopsy. Fasting serum was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations using ELISA. Bio-Plex inflammatory cytokine assays were used to profile expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2, and MIP-1??.

Results

Patients with NASH had twofold higher concentration of des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P?P?P?P?=?0.014). Obestatin levels at baseline significantly correlated with rate of weight loss after bariatric surgery at various time points.

Conclusions

This study suggests that products of the GHRL gene may be important for the pathogenesis of NASH and fibrosis. Additional confirmatory studies are needed.     

Effect of hydroxylated solvents on the active constituents of Salvadora persica root “Siwak”

Previously, the antimicrobial activity of Salvadora persica was traced to benzyl isothiocyanate. In the present study known inactive compounds were isolated from extracts obtained by different solvents including β-amyrin, β-sitosterol, stigmasterol glucoside, benzyl cyanide and sulphur. However, some inactive compounds were present only in the ethanol and methanol extracts. This observation indicated that these compounds most likely are artifacts resulted from interaction with the solvents used in extraction. Pure benzyl isothiocyanate was kept with different solvents for 72?h and after TLC study they were heated under reflux for 8?h to explore the possibility of interactions. Only solvents with OH groups reacted with benzyl isothiocyanate and gave products similar to those isolated from the alcohol extracts. In conclusion extraction of S. persica with hydroxylated solvents will alter the structure of the active compound benzyl isothiocyanate and leads to loss of antimicrobial activity.     

The Impact of Oral Health on the Academic Performance of Disadvantaged Children

Objectives. We measured the impact of dental diseases on the academic performance of disadvantaged children by sociodemographic characteristics and access to care determinantsMethods. We performed clinical dental examinations on 1495 disadvantaged elementary and high school students from Los Angeles County public schools. We matched data with academic achievement and attendance data provided by the school district and linked these to the child’s social determinants of oral health and the impact of oral health on the child’s school and the parents’ school or work absences.Results. Students with toothaches were almost 4 times more likely to have a low grade point average. About 11% of students with inaccessible needed dental care missed school compared with 4% of those with access. Per 100 elementary and high school–aged children, 58 and 80 school hours, respectively, are missed annually. Parents averaged 2.5 absent days from work or school per year because of their children’s dental problems.Conclusions. Oral health affects students’ academic performance. Studies are needed that unbundle the clinical, socioeconomic, and cultural challenges associated with this epidemic of dental disease in children.Poor oral health affects systemic health with consequences that can seriously compromise quality of life and life expectancy. Oral diseases can lead to systemic diseases, emergency hospital visits, hospital stays, medications, even death. Moreover, oral disease can increase personal, societal, and financial burdens and contribute to rising health care costs in general.1Anecdotally, we know that there is an epidemic of dental diseases among disadvantaged children in Los Angeles County, as is consistently observed by health professionals and community stakeholders. To quantify this observation, we established a campus–community project with the goals of measuring this epidemic and its impact and designing appropriate intervention programs to ultimately reduce the burden of poor oral health among these children. Previously, we documented that the overall prevalence of dental caries in this population of disadvantaged children was 73% and that no important racial/ethnic differences were found between Blacks, Asians, White, and non-White or “other” Hispanics.2 One aspect of this project, which we have reported in this article, is to measure the impact of dental diseases on the academic performance of these disadvantaged children by their sociodemographic characteristics and access to care determinants.It has been suggested that objective measures of oral health should be linked to measures of social outcome to place dental conditions within a broader context that is relevant to policymakers.3 Based on the National Health Interview Survey of 1989, it has been estimated that 51 million school hours are lost yearly because of dental disease based on a 15-day recollection.4 This result has been widely cited. A Google search provided more than 57 000 hits when queried for “dental” + “51 million school hours.” According to the Thomson Scientific’s Institute for Scientific Information web of knowledge, this resource has been cited in the scientific literature 55 times. More recently, the California Health Interview Survey asked about the number of school days missed in the past year because of dental problems; the question was asked only in the survey of 2007.5 No other literature sources provide definitive estimates of the number of school hours missed because of dental problems besides that reported by Gift et al.,4 nor is there any estimation of the impact of oral health on the students’ academic achievement. Furthermore, it should be noted that the means and SDs reported by Gift et al. were acknowledged as being inaccurate, and no corrected estimates were subsequently published.6 We have provided an updated estimate of the impact of dental problems on disadvantaged children missing school and parents missing school or work based on their 1-year recall. Also, we explored the relationship of oral health with academic achievement and attendance by school level, gender, and race/ethnicity. We will report other aspects of the project elsewhere.2     

In vivo dynamic distribution of 131I-glucagon-like peptide-1 (7-36) amide in the rat studied by gamma camera.

The in vivo distribution of glucagon-like peptide-1 (7-36) amide (GLP-1) was studied in a rat model using radiolabeled GLP-1 (131I-GLP-1) depicted by a gamma-camera. The dynamic scan showed a rapid clearance from the blood circulation after an intravenous (i.v.) injection of 131I-GLP-1. After 10 min, the major part of the radioactivity was accumulated in the kidneys, whereas about 9% (of the blood value) was found in the brain. The pharmacokinetic study using 125I-GLP-1 demonstrated a rapid elimination from plasma, with a half-life of 3.3 +/- 0.6 min, a clearance of 117 +/- 15 mL/min, and a distribution volume of 557 +/- 61 mL. The elimination half-lives for the intact 125I-GLP-1 in lungs and kidneys were determined to 3.7 and 3.9 min, respectively. The metabolite GLP-1 (9-36) amide was followed in blood, lung, and kidney. All other organs assumed to contain low molecular weight fragments of GLP-1. The present study suggest that GLP-1 and/or its labeled metabolites cross the blood-brain barrier. Also the kidney plays an essential role in GLP-1 elimination after an i.v. administration, which can be of clinical interest especially in patients with kidney insufficiency who are treated with GLP-1.     

Combined estrogen and ghrelin administration decreases expression of p27<Superscript>kip1</Superscript> and proportion of isomyosin type I in the striated urethral and anal sphincters and levator ani of old ovariectomized rats

We compared estrogen and/or ghrelin effects on pelvic floor muscles in old versus young adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-beta estradiol (10 mug kg(-1)), ghrelin (2 mug kg(-1)), both, or vehicle (n = 6 x 4/group). Cytoplasmic p27(kip1) expression and isomyosin I proportion in striated urethral and anal sphincters and levator ani were measured, respectively, by Western blot analysis and gel electrophoresis with immunohistochemistry of muscle ghrelin receptors and radioimmunoassay of circulating growth hormone. In young adult rats, estrogen significantly decreased cytoplasmic p27(kip1) and isomyosin I signal intensities. In old rats, ghrelin and estrogen/ghrelin significantly decreased both intensities with greater estrogen/ghrelin effect. Ghrelin receptors were not immunostained in any muscle. Estrogen and/or ghrelin significantly increased or decreased, respectively, circulating growth hormone in old and young adult rats. Estrogen/ghrelin administration reversed pelvic floor muscle ageing changes in old ovariectomized rats through growth hormone production.