Anti-leukemic activity of microRNA-26a in a chronic lymphocytic leukemia mouse model.

Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eµ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody. This methodology has proven to be highly effective in delivering miRNA molecules into leukemic cells. Short- and long-term experiments showed that miR-26a, miR-130a and anti-miR-155 increased apoptosis after in vitro and in vivo treatment. Of this miRNA panel, miR-26a was the most effective in reducing leukemic cell expansion. Following long-term treatment, apoptosis was readily detectable by analyzing cleavage of PARP and caspase-7. These effects could be directly attributed to miR-26a, as confirmed by significant downregulation of its proven targets, namely cyclin-dependent kinase 6 and Mcl1. The results of this study are relevant to two distinct areas. The first is related to the design of a technical strategy and to the selection of CD38 as a molecular target on CLL cells, both consenting efficient and specific intracellular transfer of miRNA. The original scientific finding inferred from the above approach is that miR-26a can elicit in vivo anti-leukemic activities mediated by increased apoptosis.

A case-control study of risk factors for intraoperative suprachoroidal expulsive hemorrhage.

The authors performed a case-control study of risk factors for suprachoroidal expulsive hemorrhage (SEH); the study involved 68 SEH cases at their institution from 1981 to 1986. The authors examined 113 variables in the study group and a procedure-matched control group of 217 patients randomly selected from the 35,459 patients who underwent intraocular surgery during this period, and subjected them to bivariate and conditional logistic regression analysis. The incidence of SEH was 0.19% overall, 0.16% for lens-related procedures, 0.15% for glaucoma surgery, 0.41% for retinal and vitreous procedures, and 0.56% for keratoplasty. Statistically significant risk factors for SEH in age-adjusted bivariate analyses included: glaucoma (P less than 0.0001), increased axial length (P less than 0.0001), elevated intraocular pressure (IOP) (P less than 0.0001), generalized atherosclerosis (P = 0.007), and elevated intraoperative pulse (P = 0.0001). Conditional logistic regression analysis with frequency matching on age identified significant independent risks associated with a history of glaucoma, elevated IOP, increased axial length, and intraoperative tachycardia. One of the models predicts a 752-fold increased theoretical relative risk of SEH for a patient with axial length greater than or equal to 25.8 mm, a history of glaucoma, preoperative IOP greater than 18 mmHg, and intraoperative pulse greater than or equal to 85 beats per minute. The visual outcome after SEH was best in cases of extracapsular cataract extraction (ECCE), compared with other procedures. Results suggest that attention to multiple preoperative and intraoperative ocular and systemic variables may allow identification and prophylaxis of patients at risk for SEH.

Extracapsular cataract extraction and primary posterior chamber lens implantation.

We reviewed the charts of 420 consecutive extracapsular cataract extraction cases in which the surgeon's primary intention was to implant a posterior chamber lens. Posterior chamber lens implantation was precluded in eight cases (1.9%) because of vitreous loss or capsule dehiscence. A visual acuity of 20/40 or better was achieved by 83.8% of patients. When nonoperative causes of poor vision were eliminated, this result was achieved by 96.7% of patients. The percentage of patients achieving 20/40 or better acuity decreased with increasing age but remained constant despite varying follow-up periods. The most common complication was opacification of the posterior capsule, occurring in 25.7%; 83.8% of the complications occurred during the first two postoperative years. We conclude that extracapsular cataract extraction with primary posterior chamber lens implantation is an efficient way to restore good vision after cataract formation and that the results appear to remain stable over time.

Phacoemulsification with the Heslin/Mackool Ocusystem: a follow-up report.

The experience of one surgeon (KBH) with phacoemulsification and the Heslin/Mackool Ocusystem is reported. In a study involving 350 cases with a mean follow-up period of 20.1 months, 88.6% of the patients achieved a visual acuity result of 20/40 or better, and when nonoperative causes of poor vision were eliminated, 97.2% of the study group achieved such a result. The most common complication cited was opacification of the posterior capsule, occurring 20.0% of the time. The authors conclude that the Heslin/Mackool Ocusystem is a safe and efficient instrument for phacoemulsification.

Clinical retrospective study comparing planned extracapsular cataract extraction and phakoemulsification with and without lens implantation.

We conducted a clinical retrospective study in which the records of 350 consecutive extracapsular cataract operations were reviewed in order to compare two cataract extraction techniques: planned extracapsular cataract extraction (PECCE) and phakoemulsification (PKE) with and without intraocular lens implantation. The patients in the PKE group experienced significantly better vision overall. However, when an adjustment was made for the difference in age between patient populations there was no significant difference in the percentage of patients achieving good vision between the two groups. Similarly, there was no statistically significant difference in the total number of operative or postoperative complications. The patients in the PKE group required less time for refraction to stabilize and averaged less postoperative astigmatism. Both of these differences were statistically significant even after an adjustment was made for the difference in age between populations. The presence or absence of an intraocular lens had no effect on the findings.

Phacoemulsification with the Heslin/Mackool Ocusystem: results of a retrospective study.

One surgeon's experience with phacoemulsification and the Heslin/Mackool Ocusystem is reported. The visual results and intraoperative and postoperative complications are comparable to those reported by surgeons using other phacoemulsification instruments. The authors conclude that the Heslin/Mackool Ocusystem is an efficient instrument for phacoemulsification.