Optical coherence tomography in asteroid hyalosis

PURPOSE: To demonstrate the clinical utility of optical coherence tomography (OCT) in diagnosing macular structural abnormalities in patients with asteroid hyalosis. METHODS: Case series. RESULTS: Seven eyes of seven patients underwent OCT due to inadequate funduscopic visualization secondary to asteroid hyalosis. Fluorescein angiography and B-scan ultrasonography were conducted for two patients but failed to provide diagnostic clarity. OCT provided definitive anatomical diagnoses that included macular epiretinal membrane, macular hole, traction retinal detachment, cystoid macular edema, and drusen. On the basis of OCT-assisted diagnoses, three patients elected to undergo surgical intervention. CONCLUSION: OCT can be critical to diagnose macular conditions when retinal visualization is limited by asteroid hyalosis.     

Retinal pigment epithelium rescues vascular endothelium from retinoic acid-induced apoptosis

PURPOSE: To determine whether retinoids are capable of inducing vascular endothelial cell apoptosis and whether the presence of an intact RPE monolayer can block retinoid-induced vascular endothelial cell death. METHODS: Confluent fetal bovine aortic endothelial (FBAE) cells were incubated with various concentrations of all-trans or 9-cis retinoic acid (an analogue of 11-cis retinoic acid). Apoptosis rates were determined at 24 hours, and the effect of inhibition of protein synthesis and activation of protein kinase C on apoptosis was investigated by supplying culture medium with 0.1 mg/mL cycloheximide and 10 nM phorbol myristate acetate. To investigate the impact of RPE on retinoid-induced apoptosis, confluent FBAE cells were cultured with a confluent layer of RPE in inserts where retinoids were added to the upper compartment. A confluent bovine corneal endothelium monolayer was used as the control. The permeabilities of the RPE and bovine corneal endothelium monolayers to fluorescein (20 microg/mL) and 9-cis retinoic acid (3 x 10(-4) M) were also determined. RESULTS: 9-cis Retinoic acid induced higher rates of apoptosis in FBAE cells than did all-trans retinoic acid and the control (P = 0.004). This effect was dose-dependent, with an ED(50) of 1.4 microM (r = 0.99, P = 0.004). Cycloheximide did not inhibit 9-cis retinoic acid-induced apoptosis, but phorbol myristate acetate significantly decreased the apoptosis rate (P = 0.005). The presence of a confluent RPE monolayer reduced the 9-cis retinoic acid-induced apoptosis rate (P = 0.002), but the presence of a bovine corneal endothelial monolayer did not (P > 0.05). Both cell types established a similar diffusion barrier against fluorescein and 9-cis retinoic acid. CONCLUSIONS: 9-cis Retinoic acid is an important mediator of vascular endothelial apoptosis. A confluent monolayer of RPE can prevent endothelial cell apoptosis, and this effect is not due simply to establishment of a diffusion barrier by the RPE.     

Nitrite-modified extracellular matrix proteins deleteriously affect retinal pigment epithelial cell function and viability: a comparison study with nonenzymatic glycation mechanisms

PURPOSE: Extracellular matrix (ECM) plays an important role in the regulation of cell function. The aging process may involve chemical modifications to ECM proteins, which may contribute to the aging of the Bruch membrane and pathogenesis of age-related macular degeneration (AMD). The purpose of this study is to investigate nitrite modification of basement membrane-like proteins on RPE cell behavior as a model for the aging of the Bruch membrane in age-related eye diseases. As a comparison, retinal pigment epithelium (RPE) cell behavior on glycolaldehyde-modified matrices (GMM) was also studied. METHODS: Growth factor reduced Matrigel was reacted with nitrite or glycolaldehyde for 1 week or 12 hr, respectively. Calf RPE cells were plated on the modified matrices and examined in several ways. Attachment rates, proliferation rates, apoptosis, and necrosis were determined. Cell morphology and cell susceptibility to A2E-mediated damage was also monitored. RESULTS: Nitrite-modified matrices (NMMs) inhibited cell attachment by 65% and proliferation by 33.7% compared to 69.6% and 21.7%, respectively, by GMM. Proliferation inhibition was not significant when cells were plated at high density on GMM (3.47%) but significant on NMM (20.9%). NMM induced cell apoptosis and necrosis, but GMM induced cell apoptosis only. Both modifications inhibited RPE differentiation. RPE cells on both matrices were more susceptible to blue light mediated damage by A2E, but damage was greater on NMM. CONCLUSIONS: NMM has significant damaging effects on RPE cell function and viability that is similar to the damaging effects of GMM. These studies may have relevance to the RPE dysfunction observed during the progression of AMD.     

Oral cyclic melphalan and dexamethasone for patients with AL amyloidosis

PurposeAggressive treatment of amyloid light chain (AL) amyloidosis with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) is effective in inducing hematologic remission and clinical improvement. However, only selected patients with AL amyloidosis are eligible for HDM/SCT because of amyloid-associated organ dysfunction.Patients and MethodsWe report on 70 patients with AL amyloidosis treated with oral cyclic melphalan and dexamethasone.ResultsOf 48 evaluable patients who survived and returned for follow-up assessment, 6 patients (13%) achieved a complete hematologic response and 12 patients (25%) a partial hematologic response. Responses were non-inferior for patients receiving weekly “low-dose” dexamethasone compared with those receiving 4 day pulses. Median survival for the 70 patients has not yet been reached with a median follow-up of 17 months. Nineteen patients (27%) received additional treatment leading to improvement in survival.ConclusionMelphalan/dexamethasone can lead to hematologic responses and improvement in survival, particularly for those who can receive additional treatment for AL amyloidosis.     

Associations of physical activity with quality of life and functional ability in breast cancer patients during active adjuvant treatment: the Pathways Study

The purpose of this article is to: (1) describe out of pocket (OOP) costs among minority and Caucasian participants in the BCEI, the Breast Cancer Education Intervention, a randomized clinical trial of psychoeducational quality of life interventions for breast cancer survivors (BCS); and (2) examine the OOP burden, as measured by the proportion of income spent OOP, between the two racial/ethnic groups. We examined baseline OOP costs reported by 261 early-stage I and II breast cancer survivors who participated in the BCEI trial. Data were collected using the Breast Cancer Finances Survey and the Breast Cancer Sociodemographic and Treatment Tool. OOP costs averaged 316 per month since diagnosis. Direct medical costs were316 per month since diagnosis. Direct medical costs were 281, and direct non-medical were 66. There were no significant differences in total OOP costs or direct medical and non-medical OOP costs between minority and Caucasian BCS. Minority BCS with incomes of66. There were no significant differences in total OOP costs or direct medical and non-medical OOP costs between minority and Caucasian BCS. Minority BCS with incomes of 40,000 or less spent a greater proportion of income in total OOP and direct medical OOP costs (31.4 and 27% for BCS with incomes ≤$20,000; 19.5 and 18.8% for BCS with incomes $20,000; 19.5 and 18.8% for BCS with incomes 20,001–40,0000) compared to their Caucasian counterparts (12.6 and 9.2% for BCS with incomes ≤$20,000; 8.7 and 8.2% for BCS with incomes $20,000; 8.7 and 8.2% for BCS with incomes 20,001–40,0000). OOP costs can be a considerable burden for breast cancer survivors representing as much as 31% of monthly income depending on BCS’ income levels. Future studies can investigate how this burden affects the quality of life of breast cancer survivors, especially minorities.     

Correlation of immunophenotype with progression-free survival in patients with gastrointestinal stromal tumors treated with imatinib mesylate

BACKGROUND: The therapy for gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (IM). It is unknown whether the levels of KIT expression or the presence of CD34, smooth muscle actin (SMA), desmin, or S-100 protein predicts patient outcome from IM therapy. In the current study, the prognostic effects for KIT and other proteins (CD34, SMA, desmin, S-100) were analyzed in a series of GISTs in which protein expression was evaluated by immunohistochemical analysis (IHC). METHODS: The cases of 106 patients with GIST who were uniformly treated with IM at the study institution between December 15, 2000, and January 13, 2002 were evaluated retrospectively. The association between KIT intensity, CD34, desmin, SMA, S-100 protein, and progression-free survival (PFS) was studied. Kaplan-Meier analysis and the Cox proportional hazards regression model were used for statistical analysis. RESULTS: The majority of tumors arose from the stomach (37%), small intestine (35%), and colorectum (14%). KIT expression as determined by IHC was categorized as weak (10%), intermediate (32%), or strong (58%). Patient tumors expressed CD34 (75%), SMA (56%), desmin (1%), and S-100 protein (32%). Patients whose GIST had weak, intermediate, or strong KIT expression were found to have an 18-month PFS rate of 80%, 84%, and 69%, respectively (P = .30). The presence or absence of CD34, SMA, desmin, or S-100 protein did not appear to correlate with PFS after IM. CONCLUSIONS: Patients with the appropriate clinical presentation and KIT-positive GIST tumors appear to benefit from IM independent of the level of KIT or the expression of CD34, SMA, desmin, or S-100 protein by IHC.     

Investigating human microskin grafting technique in a new experimental model

Background

. Microskin graft technique is a possible solution for treating major burns. The goal of this study was to investigate microskin graft techniques using a new model of grafting human skin onto athymic nude mice.

Materials and methods

Twenty female nude mice were randomly divided into a research group and a control group (14 mice in the research group, six in the control group). On the 11th day after the procedure, the following parameters were investigated: percentage of epithelial coverage, degree of contracture, thickness of the epidermis, thickness of the dermis, number of blood vessels, number of melanocytes.

Results

The healing rate (epithelial coverage) of the wounds was an average of 100% (±0%) in the control group and 97% (±5%) in the research group (P > 0.05). The average degree of wound contraction in the control group was 30% compared to 63% in the research group (P < 0.01). The average thickness of the epidermis formed at the grafted site was 8.17 (±1.94)μm in the control group compared to 4.45 (±4.17)μm in the research group, at the wound margins (P > 0.05).

Conclusion

We found that the microskin graft, created by grinding a sheet of human skin, remained vital, and tissue of human origin was present at the grafted site. Our study shows that this novel method is feasible and has the advantage of enabling investigation of human skin on an animal model. Significant contracture appears to be a drawback of this technique, and we feel that the method should be improved before its clinical application on patients.     

Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses

The development of neuronal networks in the brain requires the differentiation of functional synapses. Neurobeachin (Nbea) was identified as a putative regulator of membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes. Nbea is essential for evoked transmission at neuromuscular junctions, but its role in the central nervous system has not been characterized. Here, we have studied central synapses of a newly generated gene-trap knockout (KO) mouse line at embryonic day 18, because null-mutant mice are paralysed and die perinatally. Although the overall brain architecture was normal, we identified major abnormalities of synaptic function in mutant animals. In acute slices from the brainstem, both spontaneous excitatory and inhibitory postsynaptic currents were clearly reduced and failure rates of evoked inhibitory responses were markedly increased. In addition, the frequency of miniature excitatory and both the frequency and amplitudes of miniature inhibitory postsynaptic currents were severely diminished in KO mice, indicating a perturbation of both action potential-dependent and -independent transmitter release. Moreover, Nbea appears to be important for the formation and composition of central synapses because the area density of mature asymmetric contacts in the fetal brainstem was reduced to 30% of wild-type levels, and the expression levels of a subset of synaptic marker proteins were smaller than in littermate controls. Our data demonstrate for the first time a function of Nbea at central synapses that may be based on its presumed role in targeting membrane proteins to synaptic contacts, and are consistent with the 'excitatory–inhibitory imbalance' model of autism where Nbea gene rearrangements have been detected in some patients.     

Poly(N-isopropylacrylamide-co-acrylamide) cross-linked thermoresponsive microspheres obtained from preformed polymers: Influence of the physico-chemical characteristics of drugs on their release profiles

Poly(N-isopropylacrylamide-co-acrylamide) copolymer was synthesized as an interesting thermoresponsive material possessing a phase transition temperature of around 36 degrees C in phosphate buffer, pH 7.4 (PB); the concentration was 10%, w/v. The copolymer maintains a sharp phase transition at a relatively high percentage of acrylamide. The lower critical solution temperature (LCST) of the copolymer is influenced by the concentration of copolymer solution in PB. The copolymer was transformed in thermoresponsive microspheres by chemical cross-linking of amide groups with glutaraldehyde. The key factors for the successful preparation of microspheres are the use of a concentrated polymer solution, a temperature (38 degrees C) that is high enough but lower than LCST, and a long reaction time (48h). The microspheres were characterized by optical and scanning electron microscopy, swelling/deswelling kinetics, swelling degree, and PB retention at different temperatures. Finally, the influence of hydrophilicity/hydrophobicity and the molecular weight of the drugs (propranolol, lidocaine, vitamin B(12)) on their release profile from thermoresponsive microspheres were examined. Above LCST the hydrogel matrix is in the dehydrated state and hydrophobic interactions between the hydrophobic drugs and the polymer occur, modulating the release rate of the drugs. For hydrophilic drugs, the release rate is modulated mainly by the steric interaction between the drug molecule and the matrix.