Evaluating in vivo delivery of riboflavin with coulomb-controlled iontophoresis for corneal collagen cross-linking: a pilot study.

PURPOSE: To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). METHODS: The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran T500 solution (riboflavin-dextran) and 0.1% riboflavin 5'-phosphate (riboflavin-phosphate). After systemic intramuscular anesthesia, 0.25 mL of the photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm(2) for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye without current served as control. Confocal microscopy of flat-mounted corneas was used to analyze intracorneal penetration and fluorometry was used to quantify riboflavin in the aqueous within 30 minutes of treatment. RESULTS: Instillation and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma after epithelial debridement. Transepithelial delivery of riboflavin-dextran was not efficacious. Riboflavin-phosphate was successfully delivered in both epithelium conditions. Complete saturation of the cornea was achieved using CCI after removing the epithelium, the epi-ON case allowed for limited diffusion. Increasing the time from 4 to 10 minutes greatly increased the amount of riboflavin detected in the cornea and aqueous humor. CONCLUSIONS: Coulomb-controlled iontophoresis is an effective technique for transepithelial delivery of riboflavin-phosphate into the cornea. This drug delivery method would allow clinicians to significantly shorten the time required for the CXL procedure, with or without epithelial debridement. Whether efficient crosslinking can be achieved through an intact epithelium remains to be demonstrated.

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.

Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study.

The authors compared radial steady-state free precession (SSFP) coronary magnetic resonance (MR) angiography, cartesian k-space sampling SSFP coronary MR angiography, and gradient-echo coronary MR angiography in 16 healthy adults and four pilot study patients. Standard gradient-echo MR imaging with a T2 preparatory pulse and cartesian k-space sampling was the reference technique. Image quality was compared by using subjective motion artifact level and objective contrast-to-noise ratio and vessel sharpness. Radial SSFP, compared with cartesian SSFP and gradient-echo MR angiography, resulted in reduced motion artifacts and superior vessel sharpness. Cartesian SSFP resulted in increased motion artifacts (P <.05). Contrast-to-noise ratio with radial SSFP was lower than that with cartesian SSFP and similar to that with the reference technique. Radial SSFP coronary MR angiography appears preferable because of improved definition of vessel borders.

A pilot study on subject-based comprehensive steroid profiling: novel biomarkers to detect testosterone misuse in sports.

Context:  Until now, the testosterone/epitestosterone (T/E) ratio is the main marker for detection of testosterone (T) misuse in athletes. As this marker can be influenced by a number of confounding factors, additional steroid profile parameters indicating T misuse can provide substantiating evidence of doping with endogenous steroids. The evaluation of a steroid profile is currently based upon population statistics. Since large inter-individual variations exist, a paradigm shift towards subject-based references is ongoing in doping analysis. Objective:  Proposition of new biomarkers for the detection of testosterone in sports using extensive steroid profiling and an adaptive model based upon Bayesian inference. Subjects:  6 healthy male volunteers were administered with testosterone undecanoate. Population statistics were performed upon steroid profiles from 2014 male Caucasian athletes participating in official sport competition. Design:  An extended search for new biomarkers in a comprehensive steroid profile combined with Bayesian inference techniques as used in the Athlete Biological Passport resulted in a selection of additional biomarkers that may improve detection of testosterone misuse in sports. Results:  Apart from T/E, 4 other steroid ratios (6α-OH-androstenedione/16α-OH-dehydroepiandrostenedione, 4-OH-androstenedione/16α-OH-androstenedione, 7α-OH-testosterone/7β-OH-dehydroepiandrostenedione and dihydrotestosterone/5β-androstane-3α,17β-diol) were identified as sensitive urinary biomarkers for T misuse. These new biomarkers were rated according to relative response, parameter stability, detection time and discriminative power. Conclusion:  Newly selected biomarkers were found suitable for individual referencing within the concept of the Athlete's Biological Passport. The parameters showed improved detection time and discriminative power compared to the T/E ratio. Such biomarkers can support the evidence of doping with small oral doses of testosterone.

Ascending aorta measurements as assessed by ECG-gated multi-detector computed tomography: a pilot study to establish normative values for transcatheter therapies

The aim of this study was to provide an insight into normative values of the ascending aorta in regards to novel endovascular procedures using ECG-gated multi-detector CT angiography. Seventy-seven adult patients without ascending aortic abnormalities were evaluated. Measurements at relevant levels of the aortic root and ascending aorta were obtained. Diameter variations of the ascending aorta during cardiac cycle were also considered. Mean diameters (mm) were as follows: LV outflow tract 20.3 +/- 3.4, coronary sinus 34.2 +/- 4.1, sino-tubular junction 29.7 +/- 3.4 and mid ascending aorta 32.7 +/- 3.8 with coefficients of variation (CV) ranging from 12 to 17%. Mean distances (mm) were: from the plane passing through the proximal insertions of the aortic valve cusps to the right brachio-cephalic artery (BCA) 92.6 +/- 11.8, from the plane passing through the proximal insertions of the aortic valve cusps to the proximal coronary ostium 12.1 +/- 3.7, and between both coronary ostia 7.2 +/- 3.1, minimal arc of the ascending aorta from left coronary ostium to right BCA 52.9 +/- 9.5, and the fibrous continuity between the aortic valve and the anterior leaflet of the mitral valve 14.6 +/- 3.3, CV 13-43%. Mean aortic valve area was 582.0 +/- 131.9 mm(2). The variation of the antero-posterior and transverse diameters of the ascending aorta during the cardiac cycle were 8.4% and 7.3%, respectively. Results showed large inter-individual variations in diameters and distances but with limited intra-individual variations during the cardiac cycle. A personalized approach for planning endovascular devices must be considered.

Sequential therapist interventions and the therapeutic alliance: a pilot study

(from the journal abstract) Scientific interest for the concept of alliance has been maintained and stimulated by repeated findings that a strong alliance is associated with facilitative treatment process and favourable treatment outcome. However, because the alliance is not in itself a therapeutic technique, these findings were unsuccessful in bringing about significant improvements in clinical practice. An essential issue in modern psychotherapeutic research concerns the relation between common factors which are known to explain great variance in empirical results and the specific therapeutic techniques which are the primary basis of clinical training and practice. This pilot study explored sequences in therapist interventions over four sessions of brief psychodynamic investigation. It aims at determining if patterns of interventions can be found during brief psychodynamic investigation and if these patterns can be associated with differences in the therapeutic alliance. Therapist interventions where coded using the Psychodynamic Intervention Rating Scale (PIRS) which enables the classification of each therapist utterance into one of 9 categories of interpretive interventions (defence interpretation, transference interpretation), supportive interventions (question, clarification, association, reflection, supportive strategy) or interventions about the therapeutic frame (work-enhancing statement, contractual arrangement). Data analysis was done using lag sequential analysis, a statistical procedure which identifies contingent relationships in time among a large number of behaviours. The sample includes N = 20 therapist-patient dyads assigned to three groups with: (1) a high and stable alliance profile, (2) a low and stable alliance profile and (3) an improving alliance profile. Results suggest that therapists most often have one single intention when interacting with patients. Large sequences of questions, associations and clarifications were found, which indicate that if a therapist asks a question, clarifies or associates, there is a significant probability that he will continue doing so. A single theme sequence involving frame interventions was also observed. These sequences were found in all three alliance groups. One exception was found for mixed sequences of interpretations and supportive interventions. The simultaneous use of these two interventions was associated with a high or an improving alliance over the course of treatment, but not with a low and stable alliance where only single theme sequences of interpretations were found. In other words, in this last group, therapists were either supportive or interpretative, whereas with high or improving alliance, interpretations were always given along with supportive interventions. This finding provides evidence that examining therapist interpretation individually can only yield incomplete findings. How interpretations were given is important for alliance building. It also suggests that therapists should carefully dose their interpretations and be supportive when necessary in order to build a strong therapeutic alliance. And from a research point of view, to study technical interventions, we must look into dynamic variables such as dosage, the supportive quality of an intervention, and timing. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

Training referential communicative skills to individuals with autism spectrum disorder: a pilot study

Summary. The present study reports the effects of referential communication training in individuals formally diagnosed with autism spectrum disorder (ASD). Participants were 20 children with ASD (M age = 14.3 yr., SD = 4.2; 6 girls, 14 boys) in the role of speakers and 20 control children, who acted as listeners. They were all enrolled in mainstream compulsory education. Inclusion/exclusion criteria were defined according to the clinical diagnosis of ASD, the presence or absence of additional or associated disability, previous training in referential communication, and any drug treatment. Speakers were randomly assigned to one of two groups (trained vs untrained). Linguistic age, cognitive level, and autistic symptoms were analyzed, respectively, with the Peabody Picture Vocabulary Test (PPVT), the Wechsler Intelligence Scale (WISCR or WAISIII), and the Autistic Behavior Checklist (ABC). Communicative abilities were analyzed through two indexes related to message complexity and self-regulation. The trained group was trained in referential communication tasks (task analysis, role taking, and task evaluation), while the untrained group took part in a communicative game but without any specific communicative training. The results showed that the complexity of emitted messages had improved statistically significantly in the trained group as an effect of training. Ecological referential communication is shown to be an appropriate paradigm for studying the communicative process and its products and could be used to develop and implement a training program focused on those skills in which individuals with ASD are most deficient.

Accuracy and predictability in use of AO three-dimensionally preformed titanium mesh plates for posttraumatic orbital reconstruction: a pilot study.

The aim of this study was to prospectively evaluate the accuracy and predictability of new three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction.We analyzed the preoperative and postoperative clinical and radiologic data of 10 patients with isolated blow-out orbital fractures. Fracture locations were as follows: floor (N = 7; 70%), medial wall (N = 1; 1%), and floor/medial wall (N = 2; 2%). The floor fractures were exposed by a standard transconjunctival approach, whereas a combined transcaruncular transconjunctival approach was used in patients with medial wall fractures. A three-dimensional preformed AO titanium mesh plate (0.4 mm in thickness) was selected according to the size of the defect previously measured on the preoperative computed tomographic (CT) scan examination and fixed at the inferior orbital rim with 1 or 2 screws. The accuracy of plate positioning of the reconstructed orbit was assessed on the postoperative CT scan. Coronal CT scan slices were used to measure bony orbital volume using OsiriX Medical Image software. Reconstructed versus uninjured orbital volume were statistically correlated.Nine patients (90%) had a successful treatment outcome without complications. One patient (10%) developed a mechanical limitation of upward gaze with a resulting handicapping diplopia requiring hardware removal. Postoperative orbital CT scan showed an anatomic three-dimensional placement of the orbital mesh plates in all of the patients. Volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 2.5 cm(3). There was no significant difference in volume between the reconstructed and uninjured orbits.This preliminary study has demonstrated that three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction results in (1) a high rate of success with an acceptable rate of major clinical complications (10%) and (2) an anatomic restoration of the bony orbital contour and volume that closely approximates that of the contralateral uninjured orbit.

Identifying a mutual attending frame: a pilot study of gaze interactions between therapist and couple.

Refering to systems theory, we identify a supraindividual property in interactions between therapist and couple. We use gaze directions to describe the partners' behaviors and label this property the "mutual attending frame." We propose a procedure to observe triadic interactions in a consultation setting and a method to measure mutual attending. The method is illustrated by the data analysis of two triads contrasted on measures of therapeutic alliance. We discuss the potential of this method for the description of the interactive aspects of the therapeutic alliance.

A pilot study on ocular safety and efficacy of infliximab as an antifibrotic agent after experimental filtration surgery

Purpose To evaluate the safety and efficacy of infliximab as an antifibrotic agent after experimental glaucoma filtration surgery in rabbits. Methods In a randomized, prospective, masked-observer study, 30 New Zealand Albino rabbits underwent glaucoma filtration surgery. The animals were allocated to receive either intraoperative application of infliximab (group A) or mitomycin C (MMC) at a concentration of 0.2mg/ml (group B) or balanced salt solution (BSS, control)(group C). Different infliximab doses, namely 1.0mg, 2.0mg, 3.0mg, 4.0mg, 5.0mg in 0.1ml were applied. Bleb survival and characteristics were evaluated over a 30day period. The animals were killed on postoperative day 15 and 30. Histology of the operated eyes was performed to evaluate and grade the amount of scarring in each group.Cellular density was evaluated in each case. Results Infliximab did not appear to improve the outcome of filtration surgery in this model of glaucoma filtration surgery.There was a significant decrease in cellular density in the MMC group compared to the control group (p=0.0352). There was neither a significant decrease in cellular density between the infliximab group and the control group nor between the infliximab group and the MMC group. Overall there was no difference in terms of fibrosis between the three different groups. There was slightly less inflammation in the infliximab group, but not significant. Conclusions In this study intraoperative application of infliximab does not appear to be superior to the application of MMC or a control with regard to bleb survival and fibrosis. This study however demonstrates that intraoperative application of MMC significantly reduces the cellular density of the filtration bleb.

Rivastigmine for HIV-associated neurocognitive disorders: A randomized crossover pilot study.

OBJECTIVE: To assess the efficacy and safety of rivastigmine for the treatment of HIV-associated neurocognitive disorders (HAND) in a cohort of long-lasting aviremic HIV+ patients. METHODS: Seventeen aviremic HIV+ patients with HAND were enrolled in a randomized, double-blind, placebo-controlled, crossover study to receive either oral rivastigmine (up to 12 mg/day for 20 weeks) followed by placebo (20 weeks) or placebo followed by rivastigmine. Efficacy endpoints were improvement on rivastigmine in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and individual neuropsychological scores of information processing speed, attention/working memory, executive functioning, and motor skills. Measures of safety included frequency and nature of adverse events and abnormalities on laboratory tests and on plasma concentrations of antiretroviral drugs. Analyses of variance with repeated measures were computed to look for treatment effects. RESULTS: There was no change on the primary outcome ADAS-Cog on drug. For secondary outcomes, processing speed improved on rivastigmine (Trail Making Test A: F(1,13) = 5.57, p = 0.03). One measure of executive functioning just failed to reach significance (CANTAB Spatial Working Memory [strategy]: F(1,13) = 3.94, p = 0.069). No other change was observed. Adverse events were frequent, but not different from those observed in other populations treated with rivastigmine. No safety issues were recorded. CONCLUSIONS: Rivastigmine in aviremic HIV+ patients with HAND seemed to improve psychomotor speed. A larger trial with the better tolerated transdermal form of rivastigmine is warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that rivastigmine is ineffective for improving ADAS-Cog scores, but is effective in improving some secondary outcome measures in aviremic HIV+ patients with HAND.