Light absorbing properties of indocyanine green (ICG) in solution and after adsorption to the retinal surface — an ex-vivo approach

BACKGROUND: To evaluate potential differences in light absorbing properties and stability of indocyanine green (ICG) adsorbed to the retinal surface and of ICG dissolved in water and balanced salt solution. METHODS: The retina of four human donor eyes was prepared by removing the vitreous from the retinal surface. The inner surface of the specimen was covered with two to three drops of a 0.05% or 0.15% ICG solution respectively. After 1 min, the dye was removed by careful irrigation using BSS plus. The retinal specimens were then investigated by diffuse reflection spectroscopy (UV/VIS/NIR Spectrometer Lambda 900/Perkin Elmer equipped with a PELA-1020 integrating sphere accessory) and their absorption evaluated by the Kubelka-Munk function. To control the sensitivity of the setting, diffuse reflectance spectra of ICG adsorbed to a cellulose membrane and Al(2)O(3) were measured. For comparison, absorption spectra of ICG dissolved in water and BSS plus solution were measured in relation to ICG concentration and time using an UV/VIS/NIR Spectrometer Lambda 900/Perkin Elmer. RESULTS: On the retinal surface, absorption spectra exhibited a steep increase of absorption beginning at 620 nm, with a maximum at 736 nm (0.05%) and a shoulder at 745 (0.15%) and a second maximum at approximately 800 nm for both concentrations. Repeated measurement of the retinal surface 13 days after the ICG exposure revealed no changes in the position of the maxima as compared to the initial measurements. Light absorbing properties of ICG on cellulose or Al(2)O(3) are similar to those seen on the retinal surface with respect to the pattern and location of absorption maxima. In contrast, ICG dissolved in water or BSS plus disclosed variations in absorption characteristics depending on dye concentration, solute and time of measurement. CONCLUSIONS: Absorption characteristics and stability of ICG bound to the retinal surface could be of relevance when investigating potential pathomechanisms of ICG related toxicity, which might be related not only to intraoperative but also to postoperative light exposure of patients after intravitreal use of ICG.     

Management of asthma in patients supervised by primary care physicians or by specialists.

French asthma patients may be supervised by general practitioners (GPs) and/or specialists. Therefore, this study examined asthma management in patients exclusively supervised by specialists (SPE), GPs, (GP) and both (GP+SPE group), and compared the findings. Asthma patients were consecutively recruited in 348 pharmacies. Each patient completed a questionnaire providing data on personal characteristics, asthma management, perception of disease and asthma supervision. Asthma control was measured using the Asthma Control Test. Questionnaires were linked to computerised records of medications which had been dispensed before inclusion in the study. From the 1,256 patients (mean age = 36.1 yrs, 54.3% females), 11.4, 36.6, and 52.0% were placed in the SPE, GP, and GP+SPE groups, respectively. During the previous 4 weeks, most patients in the SPE group were properly controlled (52.2 versus 26.4 and 21.5% in GP and GP+SPE groups, respectively). The SPE group made more use of fixed combinations of long-acting beta agonist and inhaled corticosteroid, while receiving less short-acting beta agonists, antitussives and antibiotics. Striking differences in symptoms and asthma management were observed according to the type of asthma supervision. The current results strongly support the need to improve the management of asthma in primary care, and the coordination of care between general practitioners and specialists.     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.     

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.     

Spray coated pellets as carrier system for mucoadhesive drug nanocrystals.

High pressure homogenization can be employed to produce drug nanocrystals with a number of advantages, like improved solubility behaviors, better drug targeting or even increased mucoadhesiveness. To obtain a controlled drug delivery system it is necessary to transform the resulting nanosuspension into a solid dosage form. The present study shows the feasibility to use a mucoadhesive nanosuspension of poorly soluble hydrocortisone acetate produced by high pressure homogenization as layering dispersion in a fluidized bed process, followed by the application of an enteric coating to achieve a controlled drug release. To point out the advantages of drug nanocrystals the new fomulation was compared with a formulation containing micronized drug. Both formulations were characterized with regard to their particle size and crystallinity by using laser diffractometry, photon correlation spectroscopy and X-ray diffraction. The pellet morphology was characterized by using the environmental scanning electron microscopy (ESEM). In the in vitro dissolution tests an accelerated dissolution velocity and an increased drug release could be shown for the pellets containing drug nanocrystals.