Effects of an oral mucosa protective formulation on chemotherapy- and/or radiotherapy-induced oral mucositis: a prospective study.

BACKGROUND: Oral mucositis (OM) associated with cancer treatment not only impairs patients' quality of life but also causes treatment delays or changes. This prospective exploratory study was conducted to evaluate the efficacy of Episil® oral liquid, which is an approved protective formulation for the oral mucosa in patients with OM. The extent of the pain-relieving effect, feeling during use, and adverse events or problems were evaluated. METHODS: In total, 10 Japanese cancer patients with OM receiving chemotherapy, pretreatment therapy for hematopoietic stem cell transplantation, or radiation therapy for head and neck cancer were enrolled. RESULTS: A numerical rating scale (NRS) was used to assess oral pain intensity due to OM. Compared to baseline, the mean NRS began to decrease at 5 min after using Episil® (7.1 ± 1.4 to 4.6 ± 2.87; p = 0.264). A significant decrease was observed in the pain score after using Episil® compared with that before using Episil®, and this effect lasted up to 120 min. The protective effects of Episil® were observed 3-5 min after application. Some patients felt slight soreness or discomfort when applying Episil®. However, this discomfort due to Episil®'s stimulation was within the allowable range and transient. No adverse events were observed in any of the cases. CONCLUSIONS: The results of this prospective study showed that Episil® could be an effective treatment to relieve oral pain in Japanese patients with moderate to severe OM, and this newly approved product might adequately support patients' oral intake. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) ( UMIN000031921 ).

Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery.

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

Injectable silicone rubber for ocular implantation after evisceration.

OBJECTIVE: To investigate the usefulness of addition type liquid silicone rubber (ATLSR) as injectable implant after evisceration to maintain the eyeball volume in an animal experiment. METHODS: Twelve adult New Zealand white rabbits were included. One eye of each rabbit was randomly selected for evisceration with the fellow eye as control. ATLSR was injected to fill the eyeball socket after evisceration. In vivo observation and photographs were performed up to 24 weeks post-op. Two rabbits were sacrificed respectively at post-operative week 1, 2, 4, 8, 12 and 24. After enucleation, the vertical, horizontal and sagittal diameters of the experimental eyeballs were measured and compared with the control eyes. Histopathological studies were performed to evaluate signs of inflammation. RESULTS: Cornea remained clear throughout the observation period despite mild epithelial edema and neovascularization. Compared to the control eyes, the experimental eyes were significantly smaller in vertical diameter (17.00±1.17 vs. 17.54±1.11 mm, P<0.001), but larger in sagittal diameter (16.85±1.48 vs. 16.40±1.38 mm, P = 0.008), and had no significant difference in horizontal diameter (17.49±1.53 vs. 17.64±1.21 mm, P = 0.34). Postoperative inflammation was observed at one week after surgery, which peaked at 2-3 weeks, then regressed gradually. At week 12 and week 24, most of the inflammatory cells disappeared with some residual plasma cells and eosinophils. CONCLUSION: Injectable addition type silicon rubber may be a good choice for ocular implantation after evisceration, maintaining eyeball volume and cosmetically satisfactory when compared to the fellow eye. Spontaneous regression of inflammation implied good biocompatibility for at least 24 weeks.

Intraocular silicone implant to treat chronic ocular hypotony: an in vivo trial.

PURPOSE: The management of chronic ocular hypotony and complicated proliferative vitreoretinopathy-related retinal detachment represents a challenge. Being non-absorbable and non-biodegradable, a silicone oil implant is expected to restore the volume and the intraocular pressure of the globe, as well as to approximate the detached retina. Further advantages could be a long-term tamponade potential, absence of toxicity, and prevention of silicone oil emulsification or anterior chamber oil-prolapse. The aim of this study was to assess the histological tolerance of the silicone oil implant in a pig model. METHODS: A seamless silicone balloon implant with optional surface modifications was developed. Mini pigs were used as experimental animals, and three variants of silicone implants with different surfaces were tested: uncoated, NCO-sP(EO-stat-PO) coated, and heparin-NCO-sP(EO-stat-PO) coated silicone implants. An extracapsular lens extraction was achieved via a standard phacoemulsification followed by a standard three-port vitrectomy. The implant was then placed in the posterior segment and filled with 5000 centistoke silicone oil. One month later, the pigs were euthanized, the eyes were enucleated, and histological specimens were prepared for microscopy. RESULTS: The analysis of the histology revealed that adverse histological changes in conjunctiva, cornea, iris, and ciliary body could be excluded in all eyes operated on regardless of which variant of implant had been employed. The retina as the implant-contacting ocular tissue showed overall good tolerance, although some inflammatory reaction and fibrous proliferation was evident in some cases. CONCLUSIONS: The silicone oil implant is a promising candidate and has the potential to fulfill clinical requirements to act as a long-term intraocular tamponade agent. The heparin-NCO-sP(EO-stat-PO) coating approach could lead to a novel bioactive surface for intraocular devices with excellent properties to hinder cell adhesion and protein adsorption, although further studies will be necessary to evaluate long-term biocompatibility and long-term resistance to biological attacks.

Soft and Firm Alloplastic Implants in Rhinoplasty: Why, When and How to Use Them: A Review of 311 Cases.

BACKGROUND: Modern rhinoplasty is not just a reduction procedure. An optimal nasal esthetic result occasionally requires augmenting the nasal tip, the dorsum or the lateral wall with autografts or alloplasts. A large number of nasal implant types have been reported in the medical literature. OBJECTIVE: The goal of this article is to demystify the role and indications of nasal implants in rhinoplasty. As well, it offers both the novice and experienced nasal surgeon a basic, simplified and organized approach to the use of soft and firm nasal implants in rhinoplasty. METHODS: This article presents the authors experience with 311 rhinoplasties using both soft and firm alloplastic implants. The indications for both types of alloplasts are discussed, the surgical technique detailed and the outcomes analyzed. RESULTS: A total of 311 nasal implant cases were reviewed. This series revealed a low incidence of postoperative infection (5.57% for soft implants and 0.1% for the firm ones). The revision rate was 2.7% for the soft implants group and 7.1% for the firm implants group. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Concomitant aneurysm detection in an intracranial dolichoectasia mouse model using a MicroFil polymer perfusion technique.

OBJECTIVE: To assess the feasibility of using MicroFil polymer perfusion to detect concomitant saccular aneurysms in an intracranial arterial dolichoectasia (IADE) model in mice, and to report detailed histomorphometric features of these aneurysms. MATERIALS AND METHODS: IADE models were created in C57/BL6 mice via microsurgical injection of 25 mU elastase into the cisterna magna. The cerebral vasculature was perfused with MicroFil polymer and harvested at 1, 3, and 7 days, and 2 and 4 weeks (n=8 for each group). IADE was defined by a tortuosity index >10 combined with a 25% increase in diameter of the A1 segment of the anterior cerebral artery (ACA), internal carotid artery (ICA), or basilar artery compared with the baseline of controls, which received heat-inactivated elastase. Saccular aneurysm occurrence rate, location, and morphological parameters were investigated using macroscopic and microscopic analysis. RESULTS: IADE was present in 95% (36/38) of the subjects, with a mortality rate of 5% (2/40). Fifteen concomitant saccular aneurysms were detected in 8 (21%) of the 38 surviving mice, including 6 at the posterior communicating artery, 1 along the ACA, 2 along the anterior communicating artery complex, 3 along the ICA, and 3 along the middle cerebral artery. Rupture was confirmed in two aneurysms. Histological examination indicated that the aneurysms develop via arterial-wall remodelling, which is characterized by internal elastic lamina disruptions and muscular layer discontinuity in the media. CONCLUSIONS: The proportion of subjects developing saccular aneurysms in addition to IADE in our mouse model is similar to the 15% of patients with IADE who have concomitant saccular aneurysms.

Two Cases of Suspected Rejection of Polydimethylsiloxane Urethral Bulking Agent.

We report the cases of 2 women who had urethral bulking injections with polydimethylsiloxane for stress urinary incontinence with intrinsic sphincter deficiency and reported initial improvement of symptoms followed by rapid return of stress urinary incontinence several weeks later associated with extrusion of the bulking material. We hypothesize this unique adverse outcome could represent immune rejection of this urethral bulking agent.

Calcitriol mediated hypercalcaemia with silicone granulomas due to cosmetic injection.

We present a case of a 41-year-old woman with medical history significant for urolithiasis presenting to our hospital for psychiatric evaluation due to worsening depression and suicidal ideations for the past 2 weeks. Initial laboratory results show hypercalcaemia of 13.5 mg/mL that led to consulting internal medicine. On further questioning, the patient admitted to cosmetic silicone injections in her buttocks which were causing calcium deposition under her skin, leading to disfigurement of the sacrum and lumbar regions. She underwent further evaluation with CT and laboratory testing, which effectively ruled out malignancy and primary hyperparathyroidism. The hypercalcaemia was diagnosed as non-PTH-dependent with high levels of 1,25-dihydroxyvitamin D and low PTH. She eventually underwent tissue biopsy confirming the presence of silicone granulomas responsible for the calcitriol-mediated hypercalcaemia. This case reminds one to keep a broad differential especially in patients with hypercalcaemia in which malignancy and primary hyperparathyroidism have been ruled out.

Changes in lens stiffness due to capsular opacification in accommodative lens refilling.

Accommodation may be restored to presbyopic lenses by refilling the lens capsular bag with a soft polymer. After this accommodative lens refilling prevention of capsular opacification is a requirement, since capsular opacification leads to a decreased clarity of the refilled lens. It has been hypothesized that capsular fibrosis causing the capsular opacification results in increased stiffness of the lens capsular bag, therewith contributing to a decrease in accommodative amplitude of the lens. However, the change in viscoelastic properties of refilled lenses due to capsular fibrosis has never been measured directly. In this study we examined natural lenses from enucleated porcine eyes and refilled lenses directly after refilling and after three months of culturing, when capsular fibrosis had developed, and determined their viscoelastic properties with a low load compression tester. Control refilled lenses were included in which capsular opacification was prevented by treatment with actinomycin D. We related lens stiffening to the degree of capsular opacification, as derived from the microscopic images taken with a confocal laser scanning microscope. Overall, the refilled lenses directly after refilling were softer than refilled lenses after three months of culturing, and refilled lenses treated with actinomycin D were softer compared with untreated refilled lenses. The degree of capsular opacification as assessed by microscopy corresponds to an increase in lens stiffness. This indicates that the viscoelastic properties of the refilled lens are influenced by capsular fibrosis and modulated by treatment of the lens epithelium. In conclusion, this study shows that the development of capsular fibrosis negatively affects the viscoelastic properties of isolated, cultured refilled lenses.

Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model.

PURPOSE: To test 2 strategies to prevent capsule opacification after accommodating lens refilling in a rhesus monkey model. SETTING: Animal laboratory and laboratory of European university medical centers. DESIGN: Experimental study. METHODS: Six rhesus monkeys had refilling of the lens capsular bag. In the first strategy, before it was filled with a silicone polymer, the capsular bag was treated with noncommercial sodium hyaluronate 1.0% containing cytotoxic substances. In the second strategy, the capsular bag was filled with clinically used sodium hyaluronate 1.0% (Healon) after treatment with actinomycin-D. Slitlamp inspection was performed during a follow-up of 40 to 50 weeks. After enucleation, magnetic resonance images were obtained and confocal fluorescence imaging was performed. RESULTS: Using the first strategy, capsule opacification developed in all eyes. Using the second strategy, 1 monkey did not develop capsule opacification after a 9-month follow-up. In a second monkey, the lens capsule remained clear for 3 months, after which the hyaluronate refill material was exchanged with a silicone polymer and capsule opacification developed. Combining these results with those in a previous study, the difference in opacification between silicone and sodium hyaluronate as refilling materials was statistically significant (P<.01). CONCLUSIONS: That no capsular bag fibrosis occurred in the presence of hyaluronate suggests that the properties of hyaluronate are the reason that remaining lens epithelial cells do not develop into fibrotic cells. The choice of a suitable lens-refilling material prevents the development of capsule opacification. FINANCIAL DISCLOSURE: Mr. Terwee was an employee of Abbott Medical Optics B.V. during the study period. No other author has a financial or proprietary interest in any material or method mentioned.

Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides.

We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides.

Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution.

PURPOSE: CAM2028, a vehicle that forms a bioadhesive lipid barrier when applied to the oral mucosa, was developed as a carrier system for local delivery of benzydamine, an NSAID used for pain relief in oral mucositis. This trial compared the analgesic effect of CAM2028 plus benzydamine (CAM2028-benzydamine) with unmedicated CAM2028 (CAM2028-control) for the treatment of oral mucositis in patients with head-and-neck cancer. METHODS: Thirty-eight study participants were enrolled during their 3rd to 4th week of radiation therapy. Participants were required to have symptomatic oral mucositis (WHO Grade 2 or above) at screening and pain scores of at least 6 on an 11-point Likert scale at screening and on each day before treatment with study medication. After undergoing radiation, patients were administered a single dose of CAM2028-control or CAM2028-benzydamine 2 days apart, in a randomized crossover fashion. Pain was assessed over the following 8 h. RESULTS: With both treatments, patients experienced a mean 40 % decrease in pain intensity at 6 h (the primary study endpoint). Both treatments resulted in significant pain relief within 5 min of application that was evident during the entire 8-h assessment period. There was no difference in pain relief between the two interventions at any time point. Both treatments were safe and well tolerated. CONCLUSIONS: CAM2028-benzydamine and CAM2028-control were both efficacious in reducing pain in patients with oral mucositis related to radiation therapy for head-and-neck cancer. Analgesic effects of both medications were immediate, clinically significant, and persistent for up to 8 h.

Osmotic drug delivery to ischemic hindlimbs and perfusion of vasculature with microfil for micro-computed tomography imaging.

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to stimulate microcirculation. The choice of delivery method for these agents is important because the route of administration profoundly affects the bioactivity and efficacy of these agents(1,2). In this article, we demonstrate how to locally administer a substance in ischemic hindlimbs by using a catheterized osmotic pump. This pump can deliver a fixed volume of aqueous solution continuously for an allotted period of time. We also present our mouse model of unilateral hindlimb ischemia induced by ligation of the common femoral artery proximal to the origin of profunda femoris and epigastrica arteries in the left hindlimb. Lastly, we describe the in vivo cannulation and ligation of the infrarenal abdominal aorta and perfusion of the hindlimb vasculature with Microfil, a silicone radiopaque casting agent. Microfil can perfuse and fill the entire vascular bed (arterial and venous), and because we have ligated the major vascular conduit for exit, the agent can be retained in the vasculature for future ex vivo imaging with the use of small specimen micro-CT(3).

Partial protection against multiple RT-SHIV162P3 vaginal challenge of rhesus macaques by a silicone elastomer vaginal ring releasing the NNRTI MC1220.

OBJECTIVES: The non-nucleoside reverse transcriptase inhibitor MC1220 has potent in vitro activity against HIV type 1 (HIV-1). A liposome gel formulation of MC1220 has previously been reported to partially protect rhesus macaques against vaginal challenge with a simian HIV (SHIV). Here, we describe the pre-clinical development of an MC1220-releasing silicone elastomer vaginal ring (SEVR), including pharmacokinetic (PK) and efficacy studies in macaques. METHODS: In vitro release studies were conducted on SEVRs loaded with 400 mg of MC1220, using simulated vaginal fluid (SVF, n = 4) and 1 : 1 isopropanol/water (IPA/H(2)O, n = 4) as release media. For PK evaluation, SEVRs were inserted into adult female macaques (n = 6) for 30 days. Following a 1 week washout period, fresh rings were placed in the same animals, which were then challenged vaginally with RT-SHIV162P3 once weekly for 4 weeks. RESULTS: SEVRs released 1.66 and 101 mg of MC1220 into SVF and IPA/H(2)O, respectively, over 30 days, the differential reflecting the low aqueous solubility of the drug. In macaque PK studies, MC1220 was consistently detected in vaginal fluid (peak 845 ng/mL) and plasma (peak 0.91 ng/mL). Kaplan-Meier analysis over 9 weeks showed significantly lower infection rates for animals given MC1220-containing SEVRs than placebo rings (hazard ratio 0.20, P = 0.0037). CONCLUSIONS: An MC1220-releasing SEVR partially protected macaques from vaginal challenge. Such ring devices are a practical method for providing sustained, coitally independent protection against vaginal exposure to HIV-1.

Safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring.

OBJECTIVES: Systemic aciclovir and its prodrug valaciclovir are effective in treating and reducing recurrences of genital herpes simplex virus (HSV) and reducing transmission. Local aciclovir delivery, if it can achieve and maintain comparable intracellular genital tract levels, may be equally effective in the treatment and suppression of genital HSV. Intravaginal ring (IVR) delivery of aciclovir may provide pre-exposure prophylaxis against HSV acquisition. METHODS: Tolerability and pharmacokinetics were evaluated in six HIV-negative women with recurrent genital HSV who switched their daily oral valaciclovir suppression to an aciclovir IVR for 7 days (n = 3) or 14 days (n = 3). Blood and cervicovaginal lavage (CVL) were collected after oral and IVR dosing to measure aciclovir concentrations and genital swabs were obtained to quantify HSV shedding by PCR. RESULTS: The rings were well tolerated. Median plasma aciclovir concentrations were 110.2 ng/mL (IQR, 85.9-233.5) 12-18 h after oral valaciclovir. Little or no drug was detected in plasma following IVR dosing. Median (IQR) CVL aciclovir levels were 127.3 ng/mL (21-660.8) 2 h after oral valaciclovir, 154.4 ng/mL (60.7-327.5) 12-18 h after oral valaciclovir and 438 ng/mL (178.5-618.5) after 7 days and 393 ng/mL (31.6-1615) after 14 days of aciclovir ring use. Median CVL aciclovir levels 2 h after oral dosing were similar to levels observed 7 (P = 0.99) and 14 (P = 0.75) days after ring use. HSV DNA was not detected in genital swabs and there was no significant change in inflammatory mediators. CONCLUSIONS: This first-in-human study demonstrated that an IVR could safely deliver mucosal levels of aciclovir similar to oral valaciclovir without systemic absorption. More intensive site-specific pharmacokinetic studies are needed to determine whether higher local concentrations are needed to achieve optimal drug distribution within the genital tract.

Thrombogenicity of a new injectable biocompatible elastomer for aneurysm exclusion, compared to expanded polytetrafluoroethylene in a human ex vivo model.

OBJECTIVES: Customized aortic repair (CAR) is a new concept for endovascular aortic aneurysm repair in which a non-polymerised elastomer is injected to fill the aneurysm sac around a balloon catheter. Amongst other variables, the thrombogenicity of the elastomer should be tested, before further clinical experiments can take place. The aim of this human ex vivo study was to measure the thrombogenicity of the elastomer and to compare it to expanded polytetrafluoroethylene (ePTFE). DESIGN AND MATERIALS: In a validated ex vivo model, non-anticoagulated blood was drawn from the antecubital veins of 10 healthy donors with a 19-gauge needle. It was drawn through elastomer tubes and through ePTFE Gore-Tex vascular grafts, both 60 cm long and with an inner diameter of 3 mm. METHODS: Fibrinopeptide A (FPA) and P-selectin expression was measured in blood samples, collected at the end of the grafts. After the experiments, the deposition of platelets and fibrin onto the grafts was visualised by scanning electron microscopy. RESULTS: For these graft types, a progressive increase in FPA production was observed in time. No significant difference was observed between the elastomer and ePTFE grafts (p > 0.05). No increase in P-selectin expression, and thereby no platelet activation, was observed in the perfusate of either grafts (p > 0.05). By scanning electron microscopy, numerous platelet aggregates were observed on the ePTFE grafts, whereas just a few adhered platelets and no aggregates were observed in the elastomer grafts. CONCLUSIONS: The elastomer in its current formulation has a low thrombogenicity, comparable to ePTFE, making it an ideal substance for endovascular aneurysm sac filling. Further research should clarify the feasibility of CAR in vivo.

Thromboresistance characterization of extruded nitric oxide-releasing silicone catheters.

Intravascular catheters used in clinical practice can activate platelets, leading to thrombus formation and stagnation of blood flow. Nitric oxide (NO)-releasing polymers have been shown previously to reduce clot formation on a number of blood contacting devices. In this work, trilaminar NO-releasing silicone catheters were fabricated and tested for their thrombogenicity. All catheters had specifications of L = 6 cm, inner diameter = 21 gauge (0.0723 cm), outer diameter = 12 gauge (0.2052 cm), and NO-releasing layer thickness = 200 ± 11 µm. Control and NO-releasing catheters were characterized in vitro for their NO flux and NO release duration by gas phase chemiluminescence measurements. The catheters were then implanted in the right and left internal jugular veins of (N = 6 and average weight = 3 kg) adult male rabbits for 4 hours thrombogenicity testing. Platelet counts and function, methemoglobin (metHb), hemoglobin (Hb), and white cell counts and functional time (defined as patency time of catheter) were monitored as measured outcomes. Nitric oxide-releasing catheters (N = 6) maintained an average flux above (2 ± 0.5) × 10(-10) mol/min/cm for more than 24 hours, whereas controls showed no NO release. Methemoglobin, Hb, white cell, and platelet counts and platelet function at 4 hours were not significantly different from baseline (α = 0.05). However, clots on controls were visibly larger and prevented blood draws at a significantly (p < 0.05) earlier time (2.3 ± 0.7 hours) into the experiment, whereas all NO-releasing catheters survived the entire 4 hours test period. Results indicate that catheter NO flux levels attenuated thrombus formation in a short-term animal model.

Silicone intubation for the treatment of epiphora in adults with presumed functional nasolacrimal duct obstruction.

PURPOSE: To evaluate the long-term efficacy of silicone intubation in adults with presumed functional nasolacrimal duct obstruction. METHODS: This retrospective cohort study reviewed adults with unilateral or bilateral epiphora and presumed functional nasolacrimal duct obstruction treated with silicone intubation and followed for signs of treatment failure (defined as persistent epiphora or need for a secondary procedure). Median time to event (failure) after silicone intubation was calculated using Kaplan-Meier survival analysis. Analysis was conducted at the level of the individual eye, with clustering by person taken in account. Cox proportional hazards models were used and adjusted for within-subject variance using a robust sandwich estimator. RESULTS: Forty-four eyes from 30 patients with isolated functional nasolacrimal duct obstruction underwent silicone intubation for epiphora. Mean time to stent removal in 40 of 44 eyes was 4.0 (±4.1) months. Mean duration from the time of stent placement to last follow-up was 2.6 (±2.0) years. Overall success after silicone intubation for resolution of symptoms was 77%. Kaplan-Meier survival analysis for time to event after silicone intubation yielded a median time of 5.7 years. Extrapolated data demonstrated a 96% success rate at 2 years and 85% success rate at 3 years and predicted approximately 50% of patients to have relief of epiphora between 5 and 6 years after silicone intubation. CONCLUSIONS: In this study, silicone intubation has good long-term success for relief of epiphora in patients with presumed functional nasolacrimal duct obstruction. This study provides important clinical information to guide management of epiphora in adults with functional nasolacrimal duct obstruction.

Macular buckling for eyes with myopic foveoschisis secondary to posterior staphyloma.

PURPOSE: To determine the effectiveness of macular buckling in eyes with myopic foveoschisis and describe two methods of macular buckling: hard silicone implant and Ando plombe. METHODS: Sixteen eyes of 16 consecutive patients with myopic foveoschisis who underwent surgery with the macular buckling procedure were studied. Pars plana vitrectomy combined with macular buckling with hard silicone implant was used in 6 eyes, whereas the other 10 eyes underwent pars plana vitrectomy and macular buckling with the Ando macular plombe. RESULTS: Macular buckling, with both hard silicone implant and macular plombe resulted in reduction of retinal thickness in all patients. Best-corrected visual acuity improved in 14 of 16 eyes (87.5%), whereas it remained stable or decreased in 2 eyes (12.5%). Mean preoperative best-corrected visual acuity was 20/125 (mean logarithm of the minimal angle of resolution 0.8), whereas mean postoperative best-corrected visual acuity improved to 20/50 (mean logarithm of the minimal angle of resolution 0.39). Both methods showed a similar rate of complications, the most frequent being the development of localized areas of retinal pigment epithelium atrophy. CONCLUSION: Combined pars plana vitrectomy and macular buckling is an effective approach to treat myopic foveoschisis with both anatomical and visual improvement. Despite a similar complication rate with both buckling techniques, macular buckling with the Ando plombe was found to be technically easier with shorter surgical times.

A new proposal to evaluate the healing of open skin wounds: volumetry / Nova proposta para avaliar cicatrização de ferida cutânea aberta: volumetria

PURPOSE: To present a new proposal to evaluate the healing of an open subcutaneous and skin wound, which we termed "volumetry". METHODS: A total of 32 circular wounds were performed in the subcutaneous tissues and skin of four feet of pigs (8 each). Each wound had about 1 cm in diameter and was 0.2 cm deep. Volume was calculated from the wound filled with saline and mass Xantopren. With the aid of a magnifying glass and local lighting, the liquid was dripped with a micropipette inside the wound until complete fullness. Volume repletion was calculated in microliters, corresponding to the volume of the wound. The mass of Xantopren was placed inside the wound to obtain a mold of the lesion. Mold volume was calculated using the formula of the volume of a cylinder closest resembling a geometric figure with mold. RESULTS: The calculation of wound volume was possible with both Xantopren and mold techniques. Volume as calculated by micropipette was 119.37 ± 30.87 microliters while the volume calculated by mold was 122.41 ± 33.90 mm3 (p=0.79). CONCLUSIONS: Volumetry in pig feet is simple and reproducible. Volumetry perfomed with saline did not differ from the volumetry with mass Xantopren. This method may be a useful tool to help evaluate the healing of open skin wounds in experimental and clinical research.

OBJETIVO: Apresentar nova proposta para avaliar a cicatrização de uma ferida cutânea aberta, denominada "volumetria." MÉTODOS: Foram provocadas 32 feridas circulares cutâneas, com cerca de 1 cm de diâmetro e 0.2 cm de profundidade, em quatro patas de suíno. O volume da ferida foi calculado com solução salina e massa de xantopren. O líquido foi gotejado com uma micropipeta no interior da ferida até sua completa repleção, o que foi auxiliado com uma lupa de aumento e iluminação local. O volume de repleção foi calculado em microlitros e correspondeu ao volume da ferida. A massa de xantopren foi colocada no interior da ferida para se obter um molde da lesão. O volume do molde foi calculado utilizando-se a fórmula do volume de um cilindro que foi a figura geométrica mais parecida com o molde. RESULTADOS: O cálculo do volume da ferida foi possível com as duas técnicas propostas. O volume calculado pela micropipeta foi 119.37 ± 30.8693 microlitros e o volume calculado pelo molde foi 122.4088 ± 33.8997 mm³ (p=0.79). CONCLUSÕES: A volumetria realizada em patas de suíno é um método simples, reprodutível. A volumetria realizada com líquido não diferiu da volumetria realizada com massa de Xantopren. Esse método poderá ser útil para auxiliar na análise da cicatrização da ferida cutânea aberta em trabalhos clínicos e experimentais.