Thirteen Cases of Valeryl Fentanyl in Michigan: A Call for Expanding Opioid Testing.

ABSTRACT: In this report, we describe 13 cases of drug overdose in Michigan in which valeryl fentanyl was found in postmortem blood. Valeryl fentanyl is a schedule I opioid that is rarely found in drug overdoses in the United States. Although little data exist on the mortality and morbidity associated with valeryl fentanyl, its molecular structure indicates that it would be less potent than fentanyl.When analyzing blood samples for valeryl fentanyl, samples from peripheral sites were sometimes negative for quantitative levels; however, samples from central sites in the same decedent were positive. This could indicate unique pharmacokinetics for valeryl fentanyl, which could have implications for other fentanyl analogs. Given the paucity of pharmacodynamic information, the prohibition of its use, the potential to buttress law enforcement efforts in monitoring drug trafficking trends, and to determine the efficacy of current regulations, laboratories should test for valeryl fentanyl. When testing for valeryl fentanyl, and likely other fentanyl analogs, the site of sample collection is important: central sources of blood are preferred to peripheral sources.

A Comparison of Venous versus Capillary Blood Samples when Measuring Blood Glucose Using a Point-of-Care, Capillary-Based Glucometer.

BACKGROUND: Blood glucose level (BGL) is routinely assessed by paramedics in the out-of-hospital setting. Most commonly, BGL is measured using a blood sample of capillary origin analyzed by a hand-held, point-of-care glucometer. In some clinical circumstances, the capillary sample may be replaced by blood of venous origin. Given most point-of-care glucometers are engineered to analyze capillary blood samples, the use of venous blood instead of capillary may lead to inaccurate or misleading measurements. HYPOTHESIS/PROBLEM: The aim of this prospective study was to compare mean difference in BGL between venous and capillary blood from healthy volunteers when measured using a capillary-based, hand-held, point-of-care glucometer. METHODS: Using a prospective observational comparison design, 36 healthy participants provided paired samples of blood, one venous and the other capillary, taken near simultaneously. The BGL values were similar between the two groups. The capillary group had a range of 4.3mmol/l, with the lowest value being 4.4mmol/l and 8.7mmol/l the highest. The venous group had a range of 2.7mmol/l, with the lowest value being 4.1mmol/l and 7.0mmol/l the highest.For the primary research question, the mean BGL for the venous sample group was 5.3mmol/l (SD = 0.6), compared to 5.6mmol/l (SD = 0.8) for the capillary group. This represented a statistically significant difference of 0.3mmol/l (P = .04), but it did not reach the a priori established point of clinical significance (1.0mmol/l). Pearson's correlation coefficient for capillary versus venous indicated moderate correlation (r = 0.42). CONCLUSION: In healthy, non-fasted people in a non-clinical setting, a statistically significant, but not clinically significant, difference was found between venous- and capillary-derived BGL when measured using a point-of-care, capillary-based glucometer. Correlation between the two was moderate. In this context, using venous samples in a capillary-based glucometer is reasonable providing the venous sample can be gathered without exposure of the clinician to risk of needle-stick injury. In clinical settings where physiological derangement or acute illness is present, capillary sampling would remain the optimal approach.

Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study.

IMPORTANCE: This dose-blinded extension of the phase 2 BOLD (BAF312 on MRI Lesion Given Once Daily) Study in relapsing-remitting multiple sclerosis provides evidence on disease activity and safety of a range of siponimod doses for up to 24 months. OBJECTIVE: To assess the safety and efficacy of siponimod for up to 24 months during the dose-blinded extension of the BOLD Study. DESIGN, SETTING, AND PARTICIPANTS: At extension baseline in a randomized clinical trial, patients taking siponimod continued at the originally assigned dose and patients taking placebo were rerandomized to the 5 siponimod doses. Initial treatment was titrated over 10 days. A total of 252 eligible patients were treated at specialized multiple sclerosis centers for this study conducted from August 30, 2010, through June 3, 2013. INTERVENTIONS: Siponimod at 10-mg, 2-mg, 1.25-mg, 0.5-mg, and 0.25-mg doses. MAIN OUTCOMES AND MEASURES: Safety assessment included blood tests, documentation of adverse events at regular scheduled visits and Holter monitoring; key efficacy measures were annualized relapse rate and magnetic resonance imaging lesion activity. RESULTS: Among the 252 eligible patients, the mean (SD) ages were 37.2 (8.4) years, 35.2 (9.1) years, 34.0 (7.6) years, 35.1 (9.2) years, and 36.8 (9.1) years in the 0.25-mg, 0.5-mg, 1.25-mg, 2-mg, and 10-mg groups. Of the 252 patients, 184 (73%) entered the extension and received siponimod (10 mg: n = 33; 2 mg: n = 29; 1.25 mg: n = 43; 0.5 mg: n = 29; and 0.25 mg: n = 50); 159 (86.4%) completed the dose-blinded extension. The incidence of adverse events was similar across treatment groups (10 mg: 87.9%; 2 mg: 89.7%; 1.25 mg: 88.4%; 0.5 mg: 96.6%; and 0.25 mg: 84.0%). Nine patients reported serious adverse events (2 mg: 3/29 [10.3%], 1.25 mg: 1/43 [2.3%], 0.5 mg: 4/29 [13.8%], and 0.25 mg: 1/50 [2.0%]; no serious adverse event was reported for more than 1 patient and no new safety signals occurred compared with the BOLD Study. Dose titration mitigated symptomatic bradycardic events. Reductions in mean (95% CI) gadolinium-enhancing T1 lesion counts from the last BOLD assessment were sustained in the 10-mg, 2-mg, 1.25-mg, and 0.5-mg dose groups (0 [0-0], 0.1 [0-1.9], 0.1 [0-2.6], and 0.1 [0-2.8] at month 24, respectively). At the 3 highest vs 2 lowest doses, the estimated new/newly enlarging T2 lesion counts (95% CIs) were lower during months 6 to 12 (0.5 [0.2-1.3], 0.4 [0.2-1.1], and 0.2 [0.1-0.6] vs 1.3 [0.6-2.8] and 1.4 [0.7-2.7]), months 12 to 18 (0.4 [0.1-1.1], 0.4 [0.1-1.3], and 0.4 [0.2-1.0] vs 1.0 [0.4-2.6] and 3.6 [1.7-7.6]), and months 18 to 24 (0 [0-not estimable], 0.9 [0.1-7.6], and 0.1 [0-1.7] vs 1.6 [0.3-7.7] and 2.0 [0.4-9.5]). Annualized relapse rates (95% CIs) up to month 24 were similarly lower for the 3 highest doses: 0.22 (0.12-0.40) for 10 mg, 0.20 (0.10-0.38) for 2 mg, and 0.14 (0.08-0.26) for 1.25 mg vs 0.33 (0.19-0.56) for 0.5 mg and 0.33 (0.21-0.50) for 0.25 mg. CONCLUSIONS AND RELEVANCE: For up to 24 months of siponimod treatment, multiple sclerosis disease activity was low and there were no new safety signals; investigation in phase 3 trials is encouraged. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01185821.

Elemental Characterization and Discrimination of Nontoxic Ammunition Using Scanning Electron Microscopy with Energy Dispersive X-Ray Analysis and Principal Components Analysis.

Concerns over the toxic by-products produced by traditional ammunition have led to an increase in popularity of nontoxic ammunition. In this work, the chemical composition of six brands of nontoxic ammunition was investigated and compared to that of a road flare, which served as an environmental source with similar composition. Five rounds of each brand were fired while a further five were disassembled and the primer alone was fired. Particles collected from all samples, including the road flare, were analyzed by scanning electron microscopy with energy dispersive X-ray analysis. Common elements among the different ammunition brands included aluminum, potassium, silicon, calcium, and strontium. Spectra were then subjected to principal components analysis in which association of the primer to the intact ammunition sample was generally possible, with distinction among brands and from the road flare sample. Further, PCA loadings plots indicated the elements responsible for the association and discrimination observed.

Ropinirole in patients with restless legs syndrome and baseline IRLS total scores ≥ 24: efficacy and tolerability in a 26-week, double-blind, parallel-group, placebo-controlled study followed by a 40-week open-label extension.

BACKGROUND: As with studies of other dopamine agonists, previously reported studies of ropinirole in restless legs syndrome (RLS) recruited patients with baseline International Restless Legs Scale (IRLS) total scores ≥ 15. The reported pooled analyses of clinical trials data suggest benefits of ropinirole in patients with IRLS total scores ≥ 24, but the effects of ropinirole have not been prospectively evaluated in this patient population. OBJECTIVE: The goal of this study was to evaluate the efficacy and tolerability of ropinirole in patients with RLS and baseline IRLS total scores ≥ 24. This study was conducted in part to fulfill a postlicensing commitment between the maker of ropinirole and the European Union's Committee for Medicinal Products for Human Use. METHODS: The protocol for this study comprised a randomized, double-blind, placebo-controlled, parallel-group, 26-week phase during which adults with baseline IRLS total scores ≥ 24 received a ropinirole dose from 0.25 to 4 mg (n = 197) or placebo (n = 207) followed by a 40-week, open-label phase during which all patients (n = 269) received ropinirole. The primary efficacy end point was the change from baseline in the IRLS total score at week 12. Tolerability measures included the incidence of adverse events, augmentation, and early morning rebound. Due to the possibility of a treatment-by-center group interaction (P = 0.04) in the IRLS analysis, further efficacy exploratory analyses were performed to assess the impact of the interaction on the overall assessment of efficacy. RESULTS: Demographic characteristics were comparable between groups (mean [SD] age: placebo, 56.1 [11.38] years; ropinirole, 56.5 [11.92] years; 63% female in both groups). All of the patients in the ropinirole group were white; 99% of the placebo group was white. Ropinirole was significantly better than placebo for change from baseline in the IRLS total score during both short- and long-term treatment, with mean treatment differences of -2.1 (P = 0.039) and -2.5 (P = 0.023) for weeks 12 and 26, respectively. A statistically significant treatment by center group interaction was observed (P = 0.040) for the change from baseline in IRLS total score, indicating variation of treatment effects among center groups; however, all center groups showed an improvement from baseline at both week 12 and week 26 for the ropinirole immediate-release group and the placebo group. The incidences of augmentation and early morning rebound were ≤ 4% for ropinirole. The adverse event profile of ropinirole was consistent with that reported in previous clinical trials. CONCLUSIONS: In this subset of patients with RLS and a baseline IRLS total score ≥ 24, ropinirole was effective and well tolerated compared with placebo. The incidence of augmentation and early morning rebound in this study was low.

Phase-function normalization for accurate analysis of ultrafast collimated radiative transfer.

The scattering of radiation from collimated irradiation is accurately treated via normalization of phase function. This approach is applicable to any numerical method with directional discretization. In this study it is applied to the transient discrete-ordinates method for ultrafast collimated radiative transfer analysis in turbid media. A technique recently developed by the authors, which conserves a phase-function asymmetry factor as well as scattered energy for the Henyey-Greenstein phase function in steady-state diffuse radiative transfer analysis, is applied to the general Legendre scattering phase function in ultrafast collimated radiative transfer. Heat flux profiles in a model tissue cylinder are generated for various phase functions and compared to those generated when normalization of the collimated phase function is neglected. Energy deposition in the medium is also investigated. Lack of conservation of scattered energy and the asymmetry factor for the collimated scattering phase function causes overpredictions in both heat flux and energy deposition for highly anisotropic scattering media. In addition, a discussion is presented to clarify the time-dependent formulation of divergence of radiative heat flux.

Self-neglect: adaptation of a clinical tool to the practice of the medical examiner.

Self-neglect is the inability or unwillingness to provide for oneself the goods and services needed to live safely and independently. It is the most common allegation reported to Adult Protective Services agencies throughout the United States. Unfortunately, it seems that most medical examiners and their teams are not trained appropriately on self-neglect and forget to ask pertinent questions and document relevant observations. The most important aspect of self-neglect for the medical examiner is to recognize the diagnosis to avoid confusion with other forms of elder abuse, particularly neglect from a third party. In this context, a self-neglect scale could be a useful tool to assist the death investigation team. In the clinical field, a self-neglect severity scale was developed by the Consortium for Research in Elder Self-Neglect of Texas. It is here proposed that a self-neglect severity scale for medical examiners should be developed, to assist the investigative team in assessing these common cases. This scale is developed by modifying the clinical scale to adapt it to the particular needs of death investigation. This scale can help the medical examiner and his team in approaching these deaths in a systematic and comprehensive way.

Differentiation of bullet type based on the analysis of gunshot residue using inductively coupled plasma mass spectrometry.

Porcine tissue samples shot with two different types of bullets, jacketed and nonjacketed, were collected in the fresh state and throughout moderate decomposition. Wound samples were microwave-digested and analyzed using inductively coupled plasma mass spectrometry (ICP-MS) to detect all elements present at measurable levels in gunshot residue (GSR). Elements detected included antimony (Sb), barium (Ba), and lead (Pb), which are considered characteristic of GSR, as well as iron (Fe) and copper (Cu). These five elements were used to differentiate shot tissue and unshot tissue, as well as tissue shot by the two different bullet types, both in the fresh state and throughout moderate decomposition. The concentrations of Cu, Sb, and Pb were able to distinguish the two bullet types in fresh tissue samples at the 95% confidence level. Cu and Pb were able to differentiate the bullet types throughout moderate decomposition at the 99% confidence level.

PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease.

BACKGROUND: PREPARED was a randomized, parallel-group, double-blind, multicenter study to evaluate the efficacy of adjunctive ropinirole prolonged release (PR) versus immediate release (IR) in patients with advanced Parkinson's disease (PD). METHODS: Patients received once-daily PR (2-24 mg/d; n = 177) or three-times-daily IR (0.75-24 mg/d; n = 173) for 24 weeks. The primary endpoint was the proportion of patients maintaining ≥ 20% reduction from baseline in "off" time over two consecutive visits at Week 24 last observation carried forward (LOCF). RESULTS: At Week 24 LOCF, PR significantly increased the proportion of patients maintaining ≥ 20% reduction in "off" time versus IR (adjusted odds ratio: 1.82; 95% CI: 1.16, 2.86; P = 0.009). Mean (SD) doses at Week 24 LOCF were: PR, 18.6 (6.5) mg/d; IR, 10.4 (6.4) mg/d; mean (SD) reductions from baseline in levodopa (L-dopa) dose were -162 (226) mg and -113 (138) mg, respectively. Adverse events (AEs) were reported by 72% of patients in the PR group and 61% in the IR group; 12% and 9% of patients, respectively, withdrew from the study due to an AE, and 6% and 5%, respectively, reported serious AEs. CONCLUSIONS: Adjunctive PR provided a significantly greater improvement in symptom control in terms of the odds of achieving ≥ 20% maintained reduction in time spent "off" compared with IR. Interpretation may be confounded by the higher doses of PR versus IR that were achieved, in combination with lower doses of L-dopa by the study end. Despite dosing differences, the PR titration regimen was generally well tolerated, with an AE profile similar to that of IR.

Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury through activation of its receptor, Toll-like receptor 4 (TLR4). Paradoxically, TLR activation by endogenous ligands after ischemia worsens stroke damage. Here, we define a novel, protective role for TLRs after ischemia in the context of LPS preconditioning. Microarray analysis of brains collected 24 h after stroke revealed a unique set of upregulated genes in LPS-pretreated animals. Promoter analysis of the unique gene set identified an overrepresentation of type I interferon (IFN)-associated transcriptional regulatory elements. This finding suggested the presence of type I IFNs or interferon regulatory factors (IRFs), which upregulate interferon-stimulated genes. Upregulation of IFNbeta was confirmed by real-time reverse transcription-PCR. Direct administration of IFNbeta intracerebroventricularly at the time of stroke was sufficient for neuroprotection. TLR4 can induce both IFNbeta and interferon-stimulated genes through its adapter molecule Toll/interleukin receptor domain-containing adaptor-inducing IFNbeta (TRIF) and the IRF3 transcription factor. We show in oxygen glucose deprivation of cortical neurons, an in vitro model of stroke, that activation of TRIF after stroke reduces neuronal death. Furthermore, mice lacking IRF3 were not protected by LPS preconditioning in our in vivo model. Our studies constitute the first demonstration of the neuroprotective capacity of TRIF/IRF3 signaling and suggest that interferon-stimulated genes, whether induced by IFNbeta or by enhanced TLR signaling to IRF3, are a potent means of protecting the brain against ischemic damage.

Inflammation and the emerging role of the toll-like receptor system in acute brain ischemia.

BACKGROUND AND PURPOSE: Systemic administration of cytosine-guanine (CpG) oligodeoxynucleotides provides neuroprotection against subsequent cerebral ischemic injury. We examined the genomic response of leukocytes and brain cells after ischemia in the context of CpG preconditioning. METHODS: RNA was isolated from circulating leukocytes and ischemic cortex 3 and 24 hours after middle cerebral artery occlusion after CpG or saline pretreatment and subjected to microarray analysis. Genes uniquely upregulated in CpG-pretreated mice were examined for overrepresented transcriptional regulatory elements. RESULTS: CpG preconditioning induced a novel response to middle cerebral artery occlusion within circulating leukocytes that was dominated by natural killer cell-associated genes and the GATA-3 transcriptional regulatory element. Preconditioning also caused a novel brain response to stroke that was dominated by Type I interferon, interferon-associated genes, and transcriptional regulatory elements. CONCLUSIONS: CpG preconditioning invokes novel leukocyte and brain responses to stroke. In this, CpG may be a unique preconditioning agent, coordinating peripheral and brain responses to protect against ischemic injury.

Comparison of the effects of fourth-generation fluoroquinolones on corneal re-epithelialization in rabbit eyes.

BACKGROUND: Gatifloxacin and moxifloxacin ophthalmic solutions are frequently prescribed for antimicrobial prophylaxis following cataract and corneal refractive surgeries, although the use of topical antibiotics is likely to interfere with wound healing in the immediate postoperative period. A potential factor that may influence rates of wound healing or corneal re-epithelialization is how the solutions are preserved. Gatifloxacin is preserved with 0.005% benzalkonium chloride, whereas moxifloxacin is unpreserved. The purpose of this study was to evaluate the effects of commercially prepared topical gatifloxacin and moxifloxacin on corneal re-epithelialization in rabbit eyes. METHODS: In this randomized, prospective, controlled study, 17 New Zealand white rabbits underwent bilateral corneal de-epithelialization procedures using 20% alcohol contained within a 6 mm trephine. Postoperatively, eyes were randomly assigned to receive either gatifloxacin 0.3%, moxifloxacin 0.5%, or balanced salt solution (BSS) four times daily. Each 6 hours during the first 2 days, and every 12 hours thereafter slit-lamp measurements and corneal photography were performed, enabling de-epithelialized surface areas to be calculated via EPCO 2000 computer analysis. RESULTS: Gatifloxacin (n = 12) and moxifloxacin (n = 13) treated eyes had a statistically significant (p = 0.036) delay in epithelial healing relative to controls (BSS, n = 8). Healing rates of gatifloxacin and moxifloxacin treated eyes were not significantly different (p = 0.545). CONCLUSIONS: We found no significant difference in re-epithelialization rates following topical application of gatifloxacin 0.3% and moxifloxacin 0.5%. Both antibiotic solutions delayed healing compared to BSS. Our analysis suggests that there was no apparent added epithelial toxicity due to the presence of BAK in the gatifloxacin preparation.

Cerebrotendinous xanthomatosis: case report with evidence of oxidative stress.

Cerebrotendinous xanthomatosis is an autosomal recessive disorder of bile acid synthesis, characterized by mutation in the mitochondrial enzyme 27-hydroxylase that leads to an accumulation of cholestanol and cholesterol. Characterized clinically by premature bilateral cataracts, slowly progressive neurological deterioration with dementia, cerebellar and brainstem signs, peripheral neuropathy, and seizures, the disease presents pathologically with lipid granulomata with foamy histiocytes and cholesterol clefts. Replacement therapy with chenodeoxycholic acid slows progression of the disease but does not reverse neurological deficits. Here, we present the case of a 49-year-old woman diagnosed at autopsy with cerebrotendinous xanthomatosis, on the basis of bilateral Achilles tendon granulomas, and typical foamy histiocytic infiltration of the brain, most severe in the dentate nucleus, and a typical clinical presentation. To investigate the pathological manifestations of this disease further, we performed immunohistochemistry for N(epsilon)-(carboxymethyl)-lysine, an indicator of oxidative damage, and found strong labeling of cytoplasmic material within histiocytes. In summary, this case of undiagnosed cerebrotendinous xanthomatosis during life emphasizes the need for a greater awareness of the disease, and early diagnosis and treatment. Further, the involvement of oxidative stress in cerebrotendinous xanthomatosis indicates that combined therapy with chenodeoxycholic acid and antioxidants may improve clinical outcome.

Collagen shields as a drug delivery system for the fourth-generation fluoroquinolones.

PURPOSE: To evaluate the penetration of commercially available gatifloxacin and moxifloxacin into the anterior chamber of a rabbit eye using collagen shields presoaked in the antibiotics as a drug delivery system. METHODS: Collagen shields, presoaked for 10 min in commercially available solutions of gatifloxacin (diluted intravenous Tequin) or moxifloxacin (Vigamox) with the same concentration, were placed on the surface of each of the corneas of 12 rabbits for a total of 24 eyes (12 in each group). Aqueous humor samples were taken 3 and 6 h later. RESULTS: The concentrations of both antibiotics were high after 3 h (3.1 +/- 1.3 microg/ml for moxifloxacin and 2.3 +/- 0.8 microg/ml for gatifloxacin, p = 0.22). The concentration of gatifloxacin after 6 h was statistically significantly higher than for moxifloxacin (0.76 +/- 0.33 microg/ml vs. 0.29 + 0.14 microg/ml, respectively, p = 0.03). CONCLUSION: Our results suggest that collagen shields can be effective as a drug delivery system for the fourth-generation fluoroquinolones with a longer effect for gatifloxacin.

Hydrophilic acrylic intraocular lens as a drug-delivery system for fourth-generation fluoroquinolones.

PURPOSE: To evaluate the ability and safety of a hydrophilic acrylic intraocular lens (IOL) as a drug-delivery system for commercially available gatifloxacin and moxifloxacin. SETTING: David J. Apple, MD, Laboratories for Ophthalmic Research, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah, USA. METHODS: Thirty rabbits were divided into 2 similar groups. In Group A (15 rabbits, 30 eyes), hydrophilic acrylic IOLs (C-flex, Rayner Intraocular Lenses, Ltd.) presoaked for 24 hours in commercially available solutions of gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL were implanted after evacuation of the crystalline lens. Group B (15 rabbits, 30 eyes) had topical preoperative and postoperative cataract prophylaxis with gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL; IOLs that were not presoaked were also implanted after evacuation of the crystalline lenses. In both groups, aqueous humor samples were taken 4, 8, or 12 hours after IOL implantation (5 eyes at each time point) to determine the antibiotic concentrations. Clinical examinations were performed 24 hours postoperatively. RESULTS: The antibiotic concentrations in Group A (presoaked IOLs) were statistically significantly higher than those in Group B (topical) for both antibiotics in all postoperative samples except moxifloxacin at 12 hours. In both groups, there was no statistically significant difference between the concentrations of the 2 antibiotics. No eye showed signs of clinical toxicity. CONCLUSION: Results show the C-flex IOL is a safe and effective drug-delivery system for fourth-generation fluoroquinolones.

New photochromic foldable intraocular lens: preliminary study of feasibility and biocompatibility.

PURPOSE: To evaluate a new hydrophobic acrylic intraocular lens (IOL) with photochromic properties in vitro and in vivo in a rabbit model. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: The photochromic optic change of 5 study IOLs was evaluated in vitro on ultraviolet (UV) light exposure. The tests were done in the dry state and during immersion of the lenses in a balanced salt solution. Six additional IOLs were implanted in the right eye of New Zealand rabbits. The left eyes were implanted with SA60AT or SN60AT IOLs (Alcon Laboratories, 3 each). After a clinical follow-up of 6 months, the rabbits were killed and their eyes enucleated. Three study IOLs and 2 control SN60AT IOLs were evaluated in vitro on UV exposure after explantation. The other IOLs and the rabbit eyes had histopathologic examination. RESULTS: On in vitro UV light exposure, the optic of the study IOLs changed from colorless to yellow, turning again colorless on discontinuation of UV light projection. The same photochromic change was also observed on UV light exposure throughout the clinical follow-up of 6 rabbits, as well as after explantation of the IOLs. Postoperative clinical inflammatory reactions and cellular reactions on the surface of the explanted IOLs were similar in the study and control groups. No sign of untoward toxicity was observed in the histopathological sections of the rabbit eyes in all groups. CONCLUSIONS: The new photochromic IOL turned yellow only on exposure to UV light; otherwise it remained clear. This lens was also found to be biocompatible.

Evaluation of the effects of hydrodissection with antimitotics using a rabbit model of Soemmering's ring formation.

BACKGROUND: Regeneration/proliferation of lens material within the capsular bag still is the most frequent complication after cataract surgery. We aimed to evaluate the effects of hydrodissection with low doses of antimitotics on the overall regeneration/proliferation of lens material in rabbit eyes, using a model allowing the lens material to be confined to the equatorial region of the capsular bag, facilitating its quantification. METHODS: Twelve albino rabbits underwent bilateral phacoemulsification. Their eyes were randomized to receive 0.4 cc of balanced salt solution, 5-fluorouracil (12.5 mg/mL) or mitomycin C (0.1 mg/mL) during hydrodissection. They were left aphakic, so the capsulorhexis would fuse with the posterior capsule postoperatively. After 4 weeks, killing/enucleation was performed. Regeneration/proliferation of lens material within the equatorial capsular bag (Soemmering's ring) was graded from the Miyake-Apple view (0-4). Its area was also calculated (microm(2)) from direct measurements performed on histological sections. RESULTS: The capsulorhexis margin fused with the peripheral posterior capsule, so the central posterior capsule remained clear. There was no significant difference among the groups (Kruskal-Wallis test) regarding Soemmering's ring gross grading (P = 0.511), number of lens epithelial cell layers lining the inner surface of the capsular bag (P = 0.310) and Soemmering's ring microscopic cross-sectional area (P = 0.638). CONCLUSIONS: The effect of different solutions on after-cataract should be assessed in terms of overall regeneration/proliferation of lens material within the capsular bag, in addition to posterior capsule opacification. When administered in low doses during hydrodissection, 5-fluorouracil and mitomycin C did not show a significant inhibitory effect on after-cataract formation in rabbit eyes.

Acute effect of vasectomy on the function of the rat epididymal epithelium and vas deferens.

Persistent infertility after apparently successful vasectomy reversal is common. One possible etiology is epididymal epithelial dysfunction resulting in improper sperm maturation after vasectomy reversal. The epididymal epithelium secretes a number of proteins that are thought to be required for the maturation of sperm. Ligation of the vas deferens during vasectomy may affect the synthesis of some of these proteins. In the present study, the function of the epididymal epithelium was assessed at early times after vasectomy (1, 4, and 7 days) by measuring the level of mRNA of 4 secreted proteins: Crisp-1, clusterin, osteopontin, and transferrin. In addition, the site of synthesis of these proteins was determined by immunocytochemistry. The results demonstrated that the expression of Crisp-1 and clusterin, representative epididymal secretory proteins, was largely unaffected by vasectomy. However, osteopontin mRNA increased in the vas deferens in response to vasectomy. Immunocytochemical localization of osteopontin suggested that both infiltrating immune cells and deferential luminal epithelium were responsible for this up-regulation. Transferrin expression was viewed as a marker for immune cells at the site of injury. However, both the caput epididymis and deferential epithelia were found to express transferrin, in addition to immune cells. In conclusion, there appear to be only minor changes in expression of genes encoding epididymal secretory proteins acutely after vasectomy, but, not surprisingly, there was evidence of an inflammatory response after vasectomy.

Hydrophilic acrylic intraocular lens as a drug-delivery system: Pilot study.

PURPOSE: To evaluate the ability of a hydrophilic acrylic intraocular lens (IOL) to serve as a drug-delivery system for commercially available gatifloxacin and moxifloxacin. SETTING: David J. Apple, MD, Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: Hydrophilic acrylic IOLs (C-flex, Rayner Ltd.), presoaked for 24 hours in commercially available solutions of gatifloxacin (Zymar) or moxifloxacin (Vigamox), were implanted in the capsular bag of 6 rabbits for a total of 12 eyes (6 in each group). Aqueous humor samples were taken 2, 4, and 6 hours after implantation. One rabbit served as a control and had nonpresoaked C-flex IOLs implanted. At the end of the operation, 1 drop of Vigamox was applied to the right eye and 1 drop of Zymar was applied to the left eye of the control rabbit. RESULTS: High concentrations of both antibiotics were found in all the samples of the eyes implanted with the presoaked IOLs. The concentrations of the antibiotics decreased over time, but even the 6-hour sample concentrations were markedly higher than the concentrations found in the control rabbit after 4 hours. CONCLUSION: The results suggest that the Rayner C-flex IOL can be effective as a drug-delivery system for fourth-generation fluoroquinolones.

Interlenticular opacification: dual-optic versus piggyback intraocular lenses.

PURPOSE: To evaluate and compare the incidence of capsular bag opacification, particularly interlenticular opacification (ILO), in rabbit eyes implanted with a dual-optic silicone intraocular lens (IOL) or piggyback lenses. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: Ten dual-optic study IOLs (Synchrony), 10 control pairs of piggyback silicone-plate lenses, and 10 control pairs of piggyback single-piece hydrophobic acrylic lenses were implanted in the capsular bag of 30 rabbit eyes following phacoemulsification. After a 6-week follow-up, the rabbits were killed and their eyes enucleated. Anterior capsule opacification and posterior capsule opacification were graded on a 0 to 4 scale from a posterior or Miyake-Apple view. Interlenticular opacification was noted in relation to the center of the interlenticular space (periphery, paracentral, and central area) and to the number of quadrants involved. The eyes were then evaluated histopathologically. RESULTS: Postoperative inflammatory reaction was similar in all groups. Interlenticular opacification formation was statistically different among the 3 groups of lenses (ILO extension, P = .0013, and ILO extension x ILO quadrants, P = .0023; Kruskal-Wallis test). Pairwise post comparisons of ILO formation showed that the differences between the study IOL group and the silicone-plate lens group were not significant. Interlenticular opacification post comparisons between the hydrophobic acrylic lenses and the study lens or the silicone-plate lenses were significant (P = .002 and P = .001, respectively). Histopathologic examination showed extension of the proliferating cortical material from the peripheral Soemmering's ring into the interlenticular space, causing ILO, especially with the pairs of hydrophobic acrylic lenses. CONCLUSIONS: In this rabbit model, ILO was significantly associated with pairs of hydrophobic acrylic lenses implanted in the bag. This study appears to confirm clinical observations that implantation of 2 silicone-plate lenses in the bag is not associated with ILO. There was also a relative lack of ILO with the dual-optic silicone lens.