Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Preparation of controlled release anticancer agents. I: 5-Fluorouracil-ethyl cellulose microspheres

Microspheres of 5-fluorouracil have been prepared, using three grades of ethyl cellulose as wall forming materials, and utilizing a solvent evaporation technique under ambient conditions. An alcoholic solution of 5-fluorouracil and polymer was dispersed in liquid paraffin containing 33.3 per cent n-heptane. The effect of stirring rate, time of stirring, drug loading, and polymer grade on drug release in two different media were evaluated. The drug loaded particles were spherical in shape and had a diameter range of 25-200 mm and were suitable for incorporating into a gel base. Drug release studies in aqueous media, showed that acidic media provide a faster release rate than neutral media. The drug release study from an aqueous gel base preparation at pH 7.0 through a synthetic membrane was found to be promising for formulation of a gel-microsphere product for the treatment of skin lesions.     

Oxygenator exhaust capnography: a method of estimating arterial carbon dioxide tension during cardiopulmonary bypass.

An in vivo study was undertaken during hypothermic (28 degrees C) cardiopulmonary bypass to compare oxygenator exhaust capnography as a means of estimating arterial carbon dioxide tension (PaCO2) with bench blood gas analysis. A total of 123 pairs of measurements were made in 40 patients. Oxygenator exhaust capnographic measurements systematically underestimated PaCO2 measured by a bench blood gas analyzer. During the cooling and stable hypothermic phases of cardiopulmonary bypass, the relationship was reasonably accurate, but became far more variable during rewarming. Oxygenator exhaust capnography could be used as an inexpensive means of continuously monitoring PaCO2 during the cooling and stable hypothermic phases of cardiopulmonary bypass but should not be used during rewarming.     

Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin

The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.     

The prevalence and break down of narrow anterior chamber angle pathology presenting to a general ophthalmology clinic

To approximate the breakdown of narrow anterior chamber angle conditions, on general ophthalmology clinics, in the predominantly white population of the South East Kent region in the United Kingdom.A review was done of all patients attending a secondary care ophthalmology general clinic over a 3-year period. Patients were assessed with: slitlamp biomicroscopy with indentation gonioscopy; SD optical coherence tomography, Humphrey visual field analyzer, and high frequency ultrasound and categorized into various narrow angle conditions. These were: narrow Van Herrick but open angle; primary narrow angle but nonoccludable; primary angle closure suspect; primary angle closure; chronic narrow angle glaucoma; plateau iris configuration; plateau iris syndrome, and phacomorphic narrow angle.A total of 14,520 patients were referred to the clinic, of those 10,491 attended and were analyzed. Six hundred seventy four (6.4%) of the patients had some form of narrow angle condition in at least 1 eye. The majority of these patients were at relative low risk of pathology such as nonoccludable narrow angles (359/53.3%) and narrow Van Herrick but open angles (93/13.8%). 8.8% of all the narrow angle patients had primary angle closure suspect or primary angle closure. Plateau iris pathology was seen in 68 (10.1%) of patients with 18 (26%) having confirmed plateau iris syndrome after peripheral iridotomy. Phacomorphic pathology was confirmed in 75 (11.1%) patients.Narrow angle patients form a significant proportion (6.4%) of those attending general ophthalmology clinic in the predominantly white population in the South East Kent Region of the United Kingdom. The majority of these (67.1%) are at a relatively low risk of developing acute or chronic angle closure glaucoma. Of the remaining patients 8.8% have primary angle closure suspect or primary angle closure and 2.9% have already progressed to chronic narrow angle closure glaucoma. Plateau iris pathology and phacomorphic glaucoma account for the remainder of the presentations.     

Cost-effectiveness of breast cancer screening programme for women in rural China

In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.