In vitro and in vivo effects of ophthalmic solutions on silicone hydrogel bandage lens material Senofilcon A

Background

Acuvue Oasys silicone hydrogel contact lenses (Senofilcon A) are used as bandage lenses and often combined with ophthalmic solutions in the treatment of ocular diseases. Concerns have been raised regarding the compatibility and effect of eye‐drop solutions on the bandage lenses, which have led to frequent replacement of lenses causing clinical problems. Some patients experience pain or discomfort during treatments and the accumulation of drugs and preservatives in lenses has been suggested as a possible reason. The aim with this study was to investigate the effect of ophthalmic solutions on silicone hydrogel bandage lens material Senofilcon A in vitro and in vivo.

Methods

The effect of three common ophthalmic solutions Isopto‐Maxidex, Timosan and Oftaquix on Acuvue Oasys (Senofilcon A) bandage lenses was evaluated. An in vitro model method was developed where drug and preservative uptake by Acuvue Oasys was monitored with ultraviolet–visible spectroscopy and laser desorption ionisation mass spectrometry. Surface morphology changes of the lenses were evaluated using scanning electron microscopy. The method was then implemented for the in vivo pilot study evaluating lenses worn by patients.

Results

In vitro model study monitoring the drug and preservatives uptake showed that the active ingredients from all the eye drops together with preservatives were taken up by the lenses in significant amounts. For the in vivo study no traces of active ingredients or preservatives could be found on the worn and treated lenses regardless of time being worn or dosage profiles. The surface morphology changes in the in vivo study were also minor in contrast to the changes observed in the in vitro scanning electron microscopy images.

Conclusion

The in vivo results demonstrate minor effects of the ophthalmic solutions on the worn lenses. These results do not support the building up of preservatives and drugs on the contact lenses as the cause of pain or discomfort experienced by some patients, which is encouraging for the use of bandage lenses in combination with ophthalmic solutions.

     

MOSAICISM CONFINED TO PLACENTA IN PREGNANCIES WITH ADVERSE OUTCOME

Chorionic villi and feral tissues from 50 pathological human conceptions ar gesrarional weeks 9-40 were cultured and cytogenetically analyzed to explore the existence of chromosomal mosaicism confined to the extraembryonic tissues and to clarify the relationship between confined placental mosaicism and adverse outcome of pregnancy. Chorionic villi and fetal rlssues from 12 second trimester gesrations terminated for social reasons served as a control group. In two pathological gestations, true mosaicism was found exclusively in chorionic cells and could not be confirmed in cells derived from the fetal tissues, One of these was severely growth retarded, Concordant results were obtained in all other cases,     

Gastrointestinal infection among international travelers globally

Background.  Data on relative rates of acquisition of gastrointestinal infections by travelers are incomplete. The objective of this study was to analyze infections associated with oral ingestion of pathogens in international travelers in relation to place of exposure.
Methods.  We performed a multicenter, retrospective observational analysis of 6,086 travelers ill enough with any gastrointestinal infection to seek medical care at a GeoSentinel clinic after completion of travel during 2000 to 2005. We determined regional and country-specific reporting rate ratios (RRRs) in comparison to risk in northern and western Europe.
Results.  Travel to sub-Saharan Africa (RRR = 282), South America (RRR = 203), and South Asia (RRR = 890) was associated with the greatest rate of gastrointestinal infections. RRRs were moderate (25–142) for travel to Oceania, the Middle East, North Africa, Central America, the Caribbean, and Southeast Asia. RRRs were least (<28) following travel to southern, central, and eastern Europe; North America; Northeast Asia; and Australasia. Income level of the country visited was inversely proportional to the RRR for gastrointestinal infection. For bacterial and parasitic infections examined separately, the regions group in the same way. RRRs could be estimated for 28 individual countries and together with regional data were used to derive a global RRR map for travel-related gastrointestinal infection.
Conclusions.  This analysis of morbidity associated with oral ingestion of pathogens abroad determines which parts of the world currently are high-risk destinations.     

Facile radiosynthesis of fluorine-18 labeled beta-blockers. Synthesis, radiolabeling, and ex vivo biodistribution of [18F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol

An efficient and general method has been developed for fluorine-18 labeling of beta-blockers that possess the propanolamine moiety. A new synthetically versatile intermediate, 3-(1-(benzyloxy)propan-2-yl)-2-oxooxazolidin-5-yl)methyl 4-methylbenzenesulfonate (13), was prepared and can be conjugated to any phenoxy core. To demonstrate the synthetic methodology, fluorinated derivatives of toliprolol were prepared, namely, [(18)F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol ((2S and 2R)-[(18)F]1). The radiosyntheses were accomplished in <1 h, with 20-24% (uncorrected for decay, n = 7) radiochemical yields, >96% radiochemical and >99% enantiomeric purities, with specific activities of 0.9-1.1 Ci/micromol (EOS). Ex vivo biodistribution studies with the radiotracers demonstrated excessively rapid washout that may limit their use for cerebral PET imaging.     

A Systematic Overview of Radiation Therapy Effects in Cervical Cancer (Cervix Uteri)

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7 952 patients. The results were compared with those of a similar overview from 1996 including 34 024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn.There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer.There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer.The NCI has recently published an announcement stating that cisplantin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages (>IIB).There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea.There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer.There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications.     

Ototoxicity,nephrotoxicity and pharmacokinetics of cisplatin and its monohydrated complex in the guinea pig

PURPOSE: To evaluate and compare the ototoxicity and nephrotoxicity of cisplatin and cis-diammineaquachloroplatinum(II) ion (monohydrated complex of cisplatin, MHC, formed in vivo by hydrolysis of cisplatin) after their separate administration to guinea pigs. METHODS: A dose of 4 mg/kg body weight of MHC was deemed suitable for the toxicity evaluation after dose titration. Electrophysiological hearing thresholds (auditory brainstem response, ABR), plasma creatinine and weight were measured in three groups of animals before and after receiving MHC 4 mg/kg (0.0141 mmol/kg), cisplatin 4.24 mg/kg (0.0141 mmol/kg, i.e. equimolar dose) or cisplatin 8 mg/kg (0.0267 mmol/kg) as an i.v. bolus injection. Cisplatin and MHC were analysed using liquid chromatography with post-column derivatization. RESULTS: Administration of MHC 4 mg/kg caused a moderate ABR threshold shift, a significant increase in creatinine and a significant weight loss, changes similar to those seen after administration of cisplatin 8 mg/kg. Animals given cisplatin 4.24 mg/kg had a slight increase in creatinine, but had no ABR threshold shift and gained weight during the experiment. The pharmacokinetic parameters of cisplatin and MHC were estimated after administration of cisplatin 4.24 mg/kg and MHC 4 mg/kg. The area under the blood-ultrafiltrate concentration versus time curve (AUC) for cisplatin after administration of MHC 4 mg/kg was 23% (56+/-5.0 micro g.min.ml(-1)) (means+/-SD) of that after administration of cisplatin 4.24 mg/kg (240+/-25 micro g.min.ml(-1)). The AUC for MHC after administration of cisplatin 4.24 mg/kg was 20% (30+/-4.9 micro g.min.ml(-1)) of that after administration of MHC 4 mg/kg (149+/-26 micro g.min.ml(-1)). CONCLUSIONS: MHC 4 mg/kg causes ototoxicity, nephrotoxicity and weight loss when administered to guinea pigs. The toxic effects were similar to those seen after administration of cisplatin 8 mg/kg and higher than those seen after administration of cisplatin 4.24 mg/kg.     

Target-focused medical emergency team training using a human patient simulator: effects on behaviour and attitude

CONTEXT: Full-scale simulation training is an accepted learning method for gaining behavioural skills in team-centred domains such as aviation, the nuclear power industry and, recently, medicine. In this study we evaluated the effects of a simulator team training method based on targets and known principles in cognitive psychology. METHODS: This method was developed and adapted for a medical emergency team. In particular, we created a trauma team course for novices, and allowed 15 students to practise team skills in 5 full-scale scenarios. Students' team behaviour was video-recorded and students' attitude towards safe teamwork was assessed using a questionnaire before and after team practice. RESULTS: Nine of 10 observed team skills improved significantly in response to practice, in parallel with a global rating of team skills. In contrast, no change in attitude toward safe teamwork was registered. CONCLUSION: The use of team skills in 5 scenarios in a full-scale patient simulator environment implementing a training method based on targets and known principles in cognitive psychology improved individual team skills but had no immediate effect on attitude toward safe patient care.