Bilateral late posterior chamber intraocular lens dislocation with the capsular bag in a patient with gyrate atrophy

A pseudophakic patient with gyrate atrophy of the choroid and retina presented with bilateral intraocular lens (IOL) dislocation with the capsular bag several years after uneventful cataract surgery. The patient had not performed strenuous physical activity. One IOL was initially repositioned by nonsurgical manipulations, while the other required surgical repositioning. Eventually, IOL exchange was performed successfully in both eyes.     

Eccentric capsulorhexis and postoperative dysphotopsia following phacoemulsification

We report a case of troublesome visual symptoms or dysphotopsia in a 68-year-old patient after right phacoemulsification and implantation of a 3-piece AcrySof(R) MA60BM acrylic intraocular lens (IOL) (Alcon) in the capsular bag. The patient described multiple horizontal streaks in dim lighting conditions with light sources in the right temporal visual field. The anterior capsulorhexis was eccentric, leaving the nasal optic edge and site of polypropylene haptic insertion uncovered by the semi-opaque anterior capsule and the probable source of the flare images. Miotic therapy was poorly tolerated and IOL exchange declined. The case illustrates the importance of creating a central capsulorhexis smaller than the IOL optic to reduce the risk photic phenomena and edge effect with square-edged IOLs.     

Laulimalide and paclitaxel: a comparison of their effects on tubulin assembly and their synergistic action when present simultaneously

Previous work has shown that laulimalide, a sponge-derived natural product, resembles paclitaxel in enhancing tubulin assembly and in its effects on cellular microtubules. The two compounds, however, seem to have distinct binding sites on tubulin polymer. Nearly equimolar amounts of tubulin, laulimalide, and paclitaxel are recovered from microtubules formed with both drugs. In the present study, we searched for differences between laulimalide and paclitaxel in their interactions with tubulin polymer. Laulimalide was compared with paclitaxel and epothilone A, a natural product that competes with paclitaxel in binding to microtubules, for assembly properties at different temperatures and for effects of GTP and microtubule-associated proteins on assembly. Although minor differences were observed among the three drugs, their overall effects were highly similar, except that aberrant assembly products were observed more frequently with paclitaxel and that the polymers formed with laulimalide and epothilone A were more stable at 0 degrees C. The most dramatic difference observed between laulimalide and epothilone A was that only laulimalide was able to enhance assembly synergistically with paclitaxel, as would be predicted if the two drugs bound at different sites in polymer. Because stoichiometric amounts of laulimalide and paclitaxel can cause extensive tubulin assembly, maximum synergy was observed at lower temperatures under reaction conditions in which each drug alone is relatively inactive. Laulimalide-induced assembly, like paclitaxel-induced assembly, was inhibited by drugs that inhibit tubulin assembly by binding at either the colchicine- or vinblastine-binding site. When radiolabeled GTP is present in a reaction mixture with either laulimalide or paclitaxel, nucleotide hydrolysis occurs with incorporation of radiolabeled GDP into polymer.     

An analysis of poisoning deaths in Manipal, India

To determine the various factors involved in poisoning deaths, a 10-y retrospective review of 335 cases were carried out. There was an increasing trend in number of poisoning deaths from 1993-94 to 1999-2000, followed by a decline trend the last 2 y (2001-02). Ninety-one percent of the deaths were due to self-poisoning, with 77.6% of the fatalities due to insecticide consumption. Most cases occurred during winter and in the victim's rural home. Amongst all the poisoning deaths, 249 were males and 86 were females, most in the of 20-29 y age group. Suggestions have been made for the prevention of insecticide poisoning.     

Personalized psychiatry: a realistic goal

It is becoming increasingly evident that the implementation of true personalized medicine will not come as rapidly and smoothly as initially hoped. In the aftermath of the drafting of the human genome in 2001, the popular and scientific media featured numerous commentaries heralding the approaching arrival of personalized medicine to the clinic, and describing its huge benefits for patients. Media coverage predicted a drastic transformation for the practice of medicine, second to the revolution brought about by the discovery of vaccines and antibiotics. From the perspective of another 3 years, during which substantial new insights were made into the enormous complexity of human genome variation, it seems that true personalized medicine may still be decades away for many aspects of medical treatment. Nonetheless, the prospects for implementation of at least certain elements of personalized medicine for one key discipline, psychiatry, might be relatively close and more realistic. With the correct focus, realization of some benefits of genetic patient profiling for psychiatric pharmacotherapy might be near, and in due course, lead the way for true personalized psychiatry.     

An unsupervised approach to identify molecular phenotypic components influencing breast cancer features

To discover a biological basis for clinical subgroupings within breast cancers, we applied principal components (PCs) analysis to cDNA microarray data from 36 breast cancers. We correlated the resulting PCs with clinical features. The 35 PCs discovered were ranked in order of their impact on gene expression patterns. Interestingly, PC 7 identified a unique subgroup consisting of estrogen receptor (ER); (+) African-American patients. This group exhibited global molecular phenotypes significantly different from both ER (-) African-American women and ER (+) or ER (-) Caucasian women (P < 0.001). Additional significant PCs included PC 4, correlating with lymph node metastasis (P = 0.04), and PC 10, with tumor stage (stage 2 versus stage 3; P = 0.007). These results provide a molecular phenotypic basis for the existence of a biologically unique subgroup comprising ER (+) breast cancers from African-American patients. Moreover, these findings illustrate the potential of PCs analysis to detect molecular phenotypic bases for relevant clinical or biological features of human tumors in general.     

CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 participate in the retention of normal hematopoietic stem cells within the bone marrow (BM) and their release into the circulation. Homing and engraftment of human stem cells in immunodeficient mice are dependent on cell surface CXCR4 expression and the production of BM SDF-1, which acts also as a survival factor for both human and murine stem cells. However, the role of SDF-1/CXCR4 interactions in the control of human acute myelogenous leukemia (AML) cell trafficking and disease progression is poorly understood. In this study, we report that although some AML cells do not express surface CXCR4, all AML cells tested express internal CXCR4 and SDF-1. Culture of AML cells with SDF-1 promoted their survival, whereas addition of neutralizing CXCR4 antibodies, SDF-1 antibodies, or AMD3100 significantly decreased it. Pretreatment of primary human AML cells with neutralizing CXCR4 antibodies blocked their homing into the BM and spleen of transplanted NOD/SCID/B2m(null) mice. Furthermore, weekly administrations of antihuman CXCR4 to mice previously engrafted with primary AML cells led to a dramatic decrease in the levels of human AML cells in the BM, blood, and spleen in a dose- and time-dependent manner. Interestingly, the same treatment did not affect significantly the levels of normal human progenitors engrafted into NOD/SCID mice. Taken together, our findings demonstrated the importance of the SDF-1/CXCR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.     

Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas

We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of beta-catenin and pGSK3beta, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of beta-catenin (P < 0.05) and cellular expression of pGSK3beta (P < 0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of beta-catenin.