Surgical outcomes for esotropia in children with high accommodative convergence/accommodation ratio

Purpose:To assess if high accommodative convergence/accommodation (AC/A) ratio impacts surgical outcomes in children with esotropia (ET), and evaluate the appropriate target angle in surgical dosing in the presence of high AC/A ratio.Methods:A retrospective chart review identified patients who underwent primary bilateral medial rectus (BMR) recessions for ET. Patients were excluded if follow-up was ≤2 months. Basic demographic information, visual acuity, stereopsis, alignment, and target angle for surgery were collected. High AC/A was defined as ≥10 prism diopter (Δ) deviation at near compared to distance. Outcome parameters were near and distance deviations ≤10Δ within orthophoria, and/or stereopsis postoperatively. Yates’ continuity correction, unpaired t-test, regression analysis, and one-way ANOVA were used.Results:We identified 103 patients, 23 with high AC/A and 80 with normal AC/A, preoperatively. Mean age was 4.0 ± 2.5 years. Surgical success measured by postoperative alignment was 48% and 45% in the high AC/A and normal AC/A groups, respectively (P = 1.0). There was a statistically significant difference in preoperative near deviation between high AC/A and normal AC/A groups (P = 0.0015); however, there was no significant difference in preoperative distance deviation (P = 0.061). In addition, there was not a significant difference in preoperative or postoperative stereopsis between high AC/A and normal AC/A groups (P = 0.88 and P = 0.44, respectively). There was a significant difference in the normal AC/A and high AC/A groups when target angle was directed toward preoperative near deviation as determined by one-way ANOVA (F = 170.88, P < 0.0001 and F = 14.61, P = 0.0010, respectively).Conclusion:In the setting of ET treated with BMR recession, the presence of high AC/A does not affect surgical success as measured by alignment and stereopsis. In addition, when high AC/A is present, surgical dosing with a target angle toward near deviation was found to yield the best surgical outcomes in our patient population.     

Mutational response at the splenic T-Lymphocyte hprt locus in mice treated as neonates: Contrasting effects of the carcinogens N-ethyl-N-nitrosourea,dimethylnitrosamine, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

The newborn mouse tumorigenicity assay, which involves the treatment of animals during the first two weeks after birth and monitoring tumor induction after a year, has been suggested as a cost- and time-effective alternative to the conventional two-year rodent bioassay. In order to evaluate whether or not lymphocyte hprt mutant induction is an accurate predictor of carcinogenicity in the assay, we determined the frequencies of 6-thioguanine-resistant (TG^r) lymphocytes in the spleens of mice neonatally treated with the carcinogenic mutagens N-ethyl-N-nitrosourea (ENU), dimethylnitrosamine (DMN),and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Male C57BL/6 pups were injected on post-natal days 8 and 15, and the frequency of TG^r T-lymphocytes was measured in groups of three animals, sacrificed periodically up to 31 weeks post-treatment. Compared to background frequencies of 1.1–2.9 × 10⁻⁶, mutant frequencies (MFS) reached 155.1 × 10⁻⁶ following a cumulative dose of 49 mg ENU/kg body weight and 172.3 × 10⁻⁶ following a cumulative dose of 142 mg ENU/kg. These results show that TG^r lymphocyte mutations can be induced and measured in mice treated as neonates and that the induced MFs found for mice treated neonatally with ENU are comparable with frequencies reported for the treatment of adult animals with the same chemical. In contrast, treatment with the promutagenic and procarcinogenic compounds DMN (at a maximum concentration of 10.5 mg/kg) and PhIP (26.2 mg/kg) did not result in an increase in lymphocyte MF, suggesting that reactive metabolites of these compounds may not be reaching cells that are sensitive for mutation fixation. The results indicate that the lymphocyte hprt assay may fail to predict the carcinogenicity of some test chemicals in the neonatal mouse bioassay. Environ. Mol. Mutagen. 31:243–247, 1998 © 1998 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Chemosensitization of Solid Tumors by Inhibition of Bcl-xL Expression Using DNAzyme

DNAzymes are a novel class of gene suppressors that selectively bind to an RNA substrate by Watson-Crick base pairing and cleave phosphodiester bonds. To explore the potential for therapeutic use of catalytic DNA molecules, active DNAzymes targeting the bcl-xL gene were generated through a multiplex in vitro selection. The DNAzyme-mediated down-regulation of the bcl-xL expression was demonstrated in various cancer cell lines by Western blots. Treatment of the cells with the active DNAzyme led to increases in percentage of apoptotic cells and cytochrome c release from mitochondria, a hall marker of apoptosis. When combined with chemotherapeutics such as Taxol, the DNAzyme significantly sensitised a panel of cancer cells to apoptosis as measured by cell survival assay. In Taxol-resistant cells, down-regulation of bcl-xL expression by the DNAzyme reversed the chemo-resistant phenotype of the cancer cells. In a xenograft mouse model, the DNAzyme was delivered into the tumors via an ALZET osmotic pump and shown to chemosensitize PC3 tumor when treating with Taxol. The results from the present study demonstrate that bcl-xL DNAzyme treatment facilitates apoptosis in solid tumors and suggest the potential use of bcl-xL DNAzyme in combination with chemotherapeutics for cancer therapy.     

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

We have previously shown that a large part of the D-amphetamine-induced release of dopamine in the nucleus accumbens is not associated with an increase in locomotor activity, and that "functional" dopamine release (i.e. release of dopamine associated with locomotor activity) requires the distal facilitation of noradrenergic transmission through alpha1-adrenergic receptors in the prefrontal cortex. To determine the role of monosynaptic or polysynaptic projections from the prefrontal cortex to the nucleus accumbens in these amphetamine responses, either AMPA/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 300microM), N-methyl-D-aspartate (D(-)-2-amino-5-phosphono-pentanoic acid, APV, 500microM) or metabotropic [(+)-alpha-methyl-4-carboxy-phenylglycine, MCPG, 10mM] glutamate receptor antagonists were infused through a dialysis probe in the rat nucleus accumbens. CNQX and MCPG but not APV reduced the "non-functional" release of dopamine evoked by local (3microM) and systemic D-amphetamine (2mg/kg i.p.) treatments. However, the locomotor hyperactivity and functional dopamine release induced by systemic D-amphetamine were abolished by MCPG, but neither by CNQX nor by APV. MCPG treatment also abolished the hyperlocomotor activity and functional dopamine release evoked by bilateral morphine injection into the ventral tegmental area. The dopamine release evoked by this morphine treatment was 16-fold lower than that induced by the systemic D-amphetamine injection, although similar behavioral activations were observed. Altogether, our results further aid the discrimination of functional and non-functional release of dopamine. We suggest that the activation of metabotropic glutamate receptors in the nucleus accumbens is required for functional dopamine release following systemic D-amphetamine injection.     

Quantitation of film coating on Zantac 75 mg tablets and Epivir HBV 100 mg tablets by ICP-AES

PURPOSE: To present a selective analytical Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method developed and validated for the quantitation of tablet film coatings containing titanium. METHODS: Tablet samples were decomposed by either digestion or dry ashing. The amount of film tablet coating was calculated based on titanium content of the sample. RESULTS: The reported ICP-AES method was accurate, precise, sensitive and linear for determination of titanium concentrations from 2.9 to 8.6 ppm. CONCLUSION: This method provides an accurate determination of the amount of coating on a tablet and has general applicability for a variety of coating formulations containing different elements.     

Basaloid squamous cell carcinoma - larynx

Basaloid squamous cell carcinoma is a rare variant of squamous cell carcinoma, Larynx has been an uncommon site of this tumour which is said to have aggressive biological behaviour with high incidence of cervical and distant metastasis along with second primary. Two cases of laryngeal basaloid squamous cell carcinoma are reported with relevant review of literature. The submucosal spread of tumour is highlighted alongwith role of preoperative radio therapy.     

Particle-Mediated Intravascular Delivery of Oligonucleotides to Tumors: Associated Biology and Lessons from Genotherapy

For a solid tumor to become life-threatening, an adequate blood supply has to be established. Although neovascularization has dire consequences for the host, it furnishes a common route through which tumors may be accessed and eradicated by drugs. The fact that a tumor's vasculature is relatively more permeable than that of healthy host tissue means selective delivery of drugs may be achieved. The role played by the cells making up the tumor vascular bed, vascular endothelial cells (VECs), has to be evaluated closely in attempts to design ways for enhancing drug delivery to solid tumors via the vasculature. The two major roles of VECs in the body, as barrier and as transport, are both highly pertinent to drug delivery. Our review examines how VECs may be manipulated in vivo to improve the selective delivery of carriers for oligonucleotide constructs to solid tumors. It also discusses how oligonucleotide drugs may be targeted against tumor VECs on the premise that by killing these cells, the tumor itself will perish. Cationic liposomes and microspheres are the major delivery vehicles discussed, with added analyses of such other nucleic acid carriers as nanospheres, dendrimers, and polyethyleneimine.     

Cationic Liposomes and Gene Therapy for Solid Tumors

Efforts in treatment have concentrated on the development of an ideal carrier for effective delivery of therapeutic agents into affected regions of a human body. Ideally, drugs would have to be delivered as close as possible, if not within, the affected cell. From its seminal production 30 years ago for the purpose of membrane research, the liposome has passed through various stages of development to become a vehicle of choice for numerous therapeutic applications. One category of these vesicles, positively charged or cationic liposomes, are commonly used for transfer of reporter and therapeutic genes into both mammalian and nonmammalian cells both in vitro and in vivo. While cationic liposomes have many advantages over other forms of delivery mechanisms, several problems hinder their efficient use. Development of a better liposomal transfection agent may indeed require a closer look at the present cationic vesicles, the biological milieu to which they are exposed, mechanisms of membrane breaching, and limitations to entry into the nucleus. This review discusses these limitations and suggests potential ways of improving liposomal delivery of genes in the context of solid tumors.