Pharmacokinetics of ibrutinib in a patient with chronic lymphocytic leukemia on hemodialysis.

Ibrutinib, an oral Bruton's tyrosine kinase inhibitor, is a key drug for the treatment of chronic lymphocytic leukemia (CLL). It is primarily metabolized by cytochrome P450 3A. However, there are no data on the pharmacokinetics of ibrutinib in patients with severe renal impairment or on hemodialysis (HD). We evaluated the pharmacokinetics of ibrutinib in a patient with CLL undergoing HD. An 84-year-old man on HD was diagnosed with CLL and was started on ibrutinib 140 mg daily. The second day of ibrutinib administration was an HD day, and its plasma concentrations before and 1, 2, 4, and 24 hours after administration were measured and found to be 0, 6.9, 28.4, 57.1, and 0 ng/mL, respectively. The maximum plasma concentration (Cmax) and time taken to reach Cmax (tmax) on days 14 and 15 of ibrutinib treatment were 64.8 ng/mL (4 hours) and 48.1 ng/mL (2 hours), respectively. Thus, we concluded that HD did not have a significant effect on the pharmacokinetics of ibrutinib in this patient. Therefore, dose adjustment of ibrutinib between HD and non-HD days is not recommended. Interestingly, we found that tmax of the drug was prolonged, and Cmax was higher on HD days compared to those on non-HD days.

Parotid lymphangioma associated with facial nerve paralysis.

Parotid lymphangioma is a relatively rare disease that is usually detected in infancy or early childhood, and which has typical features. Clinical reports of facial nerve paralysis caused by lymphangioma, however, are very rare. Usually, facial nerve paralysis in a child suggests malignancy. Here we report a very rare case of parotid lymphangioma associated with facial nerve paralysis. A 7-year-old boy was admitted to hospital with a rapidly enlarging mass in the left parotid region. Left peripheral-type facial nerve paralysis was also noted. Computed tomography and magnetic resonance imaging also revealed multiple cystic lesions. Open biopsy was undertaken in order to investigate the cause of the facial nerve paralysis. The histopathological findings of the excised tumor were consistent with lymphangioma. Prednisone (40 mg/day) was given in a tapering dose schedule. Facial nerve paralysis was completely cured 1 month after treatment. There has been no recurrent facial nerve paralysis for eight years.

TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade.

An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. However, the cation channel has not yet been unequivocally identified. Here, we report a mouse TRPM1 long form (TRPM1-L) as the cation channel. We found that TRPM1-L localization is developmentally restricted to the dendritic tips of ON BCs in colocalization with mGluR6. TRPM1 null mutant mice completely lose the photoresponse of ON BCs but not that of OFF BCs. In the TRPM1-L-expressing cells, TRPM1-L functions as a constitutively active nonselective cation channel and its activity is negatively regulated by Go in the mGluR6 cascade. These results demonstrate that TRPM1-L is a component of the ON BC transduction channel downstream of mGluR6 in ON BCs.

[Endoscopic endonasal detection of cerebrospinal fluid leakage with topical fluorescein].

We evaluated the effectiveness of intraoperative topical application of fluorescein to detect the leakage point of cerebrospinal fluid(CSF)rhinorrhea. Three patients with CSF rhinorrhea were treated with an endoscopic endonasal technique. Ten percent fluorescein was topically used for intraoperative localization of the leak site. A change of the fluorescein color from brown to green due to dilation of CSF were recognized as evidence of CSF rhinorrhea. We repeated the procedure to detect any small defects. All CSF rhinorrheas were successfully repaired by this endoscopic endonasal approach. Topical application of fluorescein is simple and sensitive for identifying intraoperative CSF rhinorrhea.

Regeneration of tracheal epithelium using a collagen vitrigel-sponge scaffold containing basic fibroblast growth factor.

OBJECTIVES: Our group has had good results in tracheal mucosal regeneration using a collagen vitrigel-sponge scaffold in an animal model. In this study, the effectiveness of this scaffold with the application of basic fibroblast growth factor (b-FGF) was investigated. METHODS: A collagen vitrigel-sponge scaffold was fabricated with simultaneous addition of b-FGF. Three types of collagen vitrigel-sponge scaffolds were made: no b-FGF, 10 ng of b-FGF, and 100 ng of b-FGF. At 3, 5, 7, and 14 days after implantation in rats, the tracheas were removed and histologically evaluated. The regeneration of mucosal epithelium and the subepithelial layer was evaluated. RESULTS: Mucosal epithelium, including pseudostratified epithelium and ciliated cells, regenerated earlier in the scaffolds when b-FGF was applied than when b-FGF was not applied. Regeneration of the subepithelial layer, infiltration of inflammatory cells and fibroblasts, and angiogenesis were promoted earlier in the scaffolds with b-FGF application. CONCLUSIONS: Our technique for tracheal reconstruction using collagen vitrigel-sponge scaffolds with b-FGF application affords a feasible approach for accelerating the regeneration of the intraluminal surface and subepithelial layer of tracheal tissue.

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model.

INTRODUCTION: Postoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging. OBJECTIVE: The goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor. METHODS: Videoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement. RESULTS: The presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection. CONCLUSION: A prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.

Optimized conditions for high-performance liquid chromatography analysis of oligosaccharides using 7-amino-4-methylcoumarin as a reductive amination reagent.

Reductive amination reaction using 7-amino-4-methylcoumarin (AMC) as a fluorescent probe enabled analyses of glycoproteins' monosaccharides and N-linked oligosaccharides. Reductive amination of N-acetylhexosamines and AMC using sodium cyanoborohydride or dimethylamine-borane complex indicated slight recovery of derivatives, but pyridine-borane achieved better recoveries. Reversed-phase high-performance liquid chromatography (HPLC) analyses of monosaccharides constituting glycoprotein glycans using fluorimetric detection revealed linearity for 0.2 fmol to 1 pmol, with less than 5% RSD quantitation reproducibility. Reversed-phase HPLC analyses of glycoprotein glycans, combined with negative-ion electrospray ionization mass spectrometry (LC-ESI-MS), enabled their structural determination. Using this highly hydrophobic reagent, AMC-labeled oligosaccharides displayed one-order to two-order higher ESI-MS intensity than derivatives labeled using other reagents.

Assessment of non-invasive chronic fungal rhinosinusitis by cone beam CT: comparison with multidetector CT findings.

OBJECTIVE: To investigate the accuracy of cone beam CT (CBCT) to diagnose non-invasive chronic fungal rhinosinusitis. METHODS: Preoperative CT evaluation of non-invasive chronic fungal rhinosinusitis was performed by CBCT (3D Accuitomo 170®) and traditional multidetector CT (MDCT) (Aquilion 32®) in 13 and 38 patients with non-invasive chronic fungal maxillary sinusitis, respectively, in different facilities. Detection of intrasinus calcification was compared between these two groups. RESULTS: Detection of intrasinus calcification in patients with non-invasive chronic fungal maxillary sinusitis was higher in the MDCT group (84.2%) than the CBCT group (46.2%). CONCLUSION: CBCT is inferior to MDCT in detection of intrasinus calcification in patients with non-invasive chronic fungal maxillary sinusitis. CBCT is frequently used in the screening of the paranasal lesion, but it is not enough to evaluate non-invasive chronic fungal maxillary sinusitis alone. STUDY DESIGN: Retrospective study.

Heparin cross-linked collagen sponge scaffolds improve functional regeneration of rat tracheal epithelium.

Tracheal epithelial cells maintain airway homeostasis by mediating mucociliary clearance. Following tracheal reconstruction, timely epithelial regeneration is required to prevent respiratory compromise and infectious diseases. To achieve rapid tracheal epithelial regeneration, a heparin cross-linked collagen sponge containing fibroblast growth factor-2 (FGF-2) was prepared as a graft for tracheal reconstruction. The heparin cross-linked sponge exhibited a high FGF-2 retaining capacity, and tracheal epithelial and mesenchymal cells cultured in this sponge containing FGF-2 showed high proliferative capacities. Subsequently, heparin-free collagen sponge scaffolds (C/F scaffold) and collagen sponge scaffolds cross-linked with 10 µg/ml heparin retained FGF-2 (C/H10/F scaffold), and were transplanted into rats with tracheal defects. Invasion of both epithelial and non-epithelial cells was greater in rats treated with the C/H10/F scaffold at 1 week post-transplantation than in rats treated with the C/F scaffold. Moreover, at 2 weeks after transplantation, improved cilia formation was observed in the C/H10/F scaffold group, with higher motility and more potent posterior-anterior flow generation than in the C/F scaffold group. These results suggest that heparin improves functional regeneration of tracheal epithelium. Copyright © 2017 John Wiley & Sons, Ltd.

Effectiveness of steroid injections for bamboo nodules: A case report.

Vocal nodules are generally caused by vocal abuse, and conservative treatments such as voice therapy have been advocated as a first-choice treatment for vocal nodules. Reports of vocal fold lesions related to autoimmune diseases, such as bamboo nodules, are rare in the literature. Here we report a very rare case of bamboo nodules in a 30-year-old woman treated by steroid injection into the vocal folds by videoendoscopic laryngeal surgery in an outpatient setting. She was successfully treated without further recurrence. This report indicates that a steroid injection into bamboo nodules might be a useful treatment option, especially in patients who have not shown any improvement after conservative treatments.

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model / Potencial regenerativo do fator básico de crescimento de fibroblastos contido em microesferas biodegradáveis de hidrogel de gelatina aplicadas após lesão de prega vocal: efeito inicial no reparo tecidual em modelo de coelho

Abstract Introduction Postoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging. Objective The goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor. Methods Videoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement. Results The presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection. Conclusion A prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.

Resumo Introdução A disfonia pós-operatória é causada principalmente por cicatrizes nas pregas vocais. Tem sido relatado que o manejo cuidadoso da cirurgia das pregas vocais reduz o risco de formação de cicatriz. No entanto, a depender da lesão da prega vocal, o tratamento da disfonia pós-operatória pode ser desafiador. Objetivo Desenvolver uma nova abordagem regenerativa profilática para o tratamento de pregas vocais lesionadas após a cirurgia, com microesferas biodegradáveis de hidrogel de gelatina como sistema de administração de medicamentos para o Fator Básico de Crescimento de Fibroblastos (bFGF). Método A cirurgia laríngea videoendoscópica foi feita para criar lesão nas pregas vocais em 14 coelhos. Imediatamente após esse procedimento, microesferas biodegradáveis de hidrogel de gelatina com bFGF foram injetadas na prega vocal. Duas semanas após a injeção, as laringes foram excisadas para avaliação da histologia das pregas vocais e do movimento da mucosa. Resultados A presença de função vibratória deficiente foi confirmada nas pregas vocais lesionadas. A histologia e a análise de imagem digital demonstraram que as pregas vocais lesionadas injetadas com microesferas de hidrogel de gelatina com bFGF apresentaram menor formação de cicatriz, em comparação com as pregas vocais lesionadas injetadas apenas com microesferas de hidrogel de gelatina ou aquelas sem injeção. Conclusão Uma injeção profilática de microesferas biodegradáveis de hidrogel de gelatina com bFGF demonstra um potencial regenerativo para pregas vocais lesionadas em um modelo de coelho.

Chemoselection combined with alternating chemoradiotherapy or surgery for hypopharyngeal cancer.

OBJECTIVES/HYPOTHESIS: In order to make possible organ preservation, since 2007 our hospital has performed induction chemotherapy (ICT) with cisplatin and 5-fluorouracil (PF) for hypopharyngeal cancer as chemoselection, followed by alternating chemoradiotherapy (ACRT) with docetaxel, cisplatin, and 5-fluorouracil in (TPF) good responders and curative surgery was used in poor responders. METHODS: Twenty-six patients with stage III to stage IVB hypopharyngeal cancer received ICT. Eleven of the patients were classified as poor responders and received curative surgery. The remaining 15 patients were classified as good responders. Three of these patients underwent curative surgery, and the remaining 12 underwent ACRT. RESULTS: The primary lesions in the 12 ACRT patients responded completely to treatment without severe late toxicities. The estimated 3-year laryngectomy-free rate for all 26 patients was 23%. The estimated 3-year overall survival rates for all 26 patients, 12 patients treated with ACRT, and 14 patients who underwent curative surgery, were 79%, 75%, and 84%, respectively. CONCLUSION: The patients who underwent ACRT showed no significant difference in overall survival compared with the patients who underwent curative surgery. All the patients were able to proceed with this series of therapy, indicating that ICT with PF could be a feasible tool for choosing good responders. Because ACRT with TPF had a high response rate and fewer severe toxicities, this treatment could be safe and have enough impact to control hypopharyngeal cancer in good responders. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1349-1353, 2016.

Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV-induced sensorineural hearing loss.

BACKGROUND: Congenital infection with human Cytomegalovirus (HCMV) is known to be a causative agent of sensorineural hearing loss (SNHL). OBJECTIVES: To clarify the nongenetic etiology of SNHL by identifying the Cytomegalovirus (CMV)-infected region in the cochleae. STUDY DESIGN: We established an animal model of SNHL by injecting neonatal Balb/c mice with intracerebral murine Cytomegalovirus (MCMV) within 24h after delivery. RESULTS: At 3 weeks of age, unilateral and bilateral SNHL were observed in 24% (5/21) and 29% (6/21) of the mice, respectively. SNHL thereafter progressed, with 79% of mice developing bilateral SNHL by 6 weeks of age. MCMV antigens and DNA were detected in the spiral ganglion, and cells surrounding the meninges and scala tympani at 1 week of age. However, both MCMV antigens and DNA had completely disappeared by 2 weeks of age. It is possible that the MCMV reached the spiral ganglion via cerebrospinal fluid as the result of meningitis, as the stria vascularis was found to be MCMV antigen negative. Myosin VI expression in the outer hair cells was lost at 3 weeks of age. MCMV and myosin VI expression disappeared before and during SNHL progression, respectively. CONCLUSIONS: There was a definite lag time between the period in which MCMV antigens/DNA-positive cells were observed and that in which SNHL developed and myosin VI-negative hair cells were observed. Further study is needed to explore the role of MCMV in the loss of myosin VI expression in the outer hair cells.

Bioengineered trachea using autologous chondrocytes for regeneration of tracheal cartilage in a rabbit model.

OBJECTIVES/HYPOTHESIS: In this study, a bioengineered trachea composed of autologous chondrocytes was developed, and its effect on cartilaginous regeneration was evaluated by implantation into tracheal defects in rabbits. STUDY DESIGN: Prospective controlled trial in an animal model. METHODS: The tracheal prosthesis used in this study was composed of polypropylene (the frame) and collagen sponge (the scaffold). Chondrocytes were harvested from the costal cartilage of rabbits and seeded into the tracheal prosthesis. The bioengineered trachea, consisting of the tracheal prosthesis with chondrocytes, was implanted into surgically created tracheal defects of rabbits in the bioengineered group, and a tracheal prosthesis without chondrocytes was implanted in the control group. RESULTS: After implantation, the presence of regenerated cartilage was observed in the bioengineered trachea but not in the tracheal prosthesis without chondrocytes. CONCLUSIONS: It was confirmed in this study that the implanted chondrocytes proliferated in an appropriate portion of the tracheal defect and that the partially resected tracheal cartilage was repaired with regenerated cartilaginous tissue into a ring-shaped form as a whole. These results demonstrate the feasibility of cartilaginous regeneration using a bioengineered trachea with autologous chondrocytes.

Regenerative process of tracheal epithelium using a collagen vitrigel sponge scaffold.

OBJECTIVES/HYPOTHESIS: Our group has developed a collagen vitrigel sponge scaffold containing basic fibroblast growth factor (b-FGF) for tracheal reconstruction. In this study, we have investigated the regenerative process of tracheal epithelium histologically and morphologically. STUDY DESIGN: A preliminary animal experiment. METHODS: A collagen vitrigel sponge scaffold was fabricated with simultaneous addition of 100 ng b-FGF. Tracheotomies were performed, and collagen vitrigel sponge scaffolds were implanted on tracheal defects in rats. At 5, 7, and 14 days after implantation, the intraluminal surface of the regenerated tracheae was observed using endoscope. Histological examination of the intraluminal regenerated trachea was performed using light microscope and scanning electron microscope. RESULTS: Endoscopic images showed epithelial regeneration at 7 days after implantation. Light microscopic examination detected stratified epithelium at 5 days, columnar cells at 7 days, and ciliated cells at 14 days after implantation. Scanning electron microscopy images showed regenerated epithelial cells at 5 and 7 days, and ciliated cells at 14 days after implantation. CONCLUSIONS: The horizontal section and luminal area of the regenerated epithelium were investigated. The epithelium was formed at 5 days, and mature cilia were found at 14 days after implantation. Epithelium of equality equivalent to normal trachea was regenerated in a rat model with collagen vitrigel-scaffold containing b-FGF at 14 days.

Efficiency of quantitative longitudinal peak systolic strain values using automated function imaging on transthoracic echocardiogram for evaluating left ventricular wall motion: new diagnostic criteria and agreement with naked eye evaluation by experienced cardiologist.

PURPOSE: To evaluate the efficiency of automated function imaging (AFI) on transthoracic echocardiogram (TTE) for detecting left ventricular (LV) wall motion (LVWM) abnormalities, we compared longitudinal peak systolic strain (LPSS) measurements using AFI with naked eye TTE evaluations by experienced cardiologists and non-experienced residents. MATERIALS AND METHODS: A total of 352 segments of LV myocardium from 22 consecutive subjects with LVWM abnormalities based on American Heart Association classifications (11 male, mean age 58 ± 14 years) on previous TTE (Vivid-7, GE) were evaluated. LPSS was measured using stored AFI data. Naked eye evaluation of LVWM was performed by 2 experienced cardiologists and 2 non-experienced residents. RESULTS: AFI successfully tracked 342 (97%) of all segments (mean LPSS -14.8 ± 8.1%). A significant strong negative correlation was observed between LV ejection fraction using method of disks and global LPSS (R=-0.8974). Temporary AFI criteria of LPSS were normal <-12; hypokinesis -12-2; and akinesis >2. Of 342 segments, 239, 87, and 16 segments were diagnosed as normal, hypokinesis, and akinesis, respectively. Level of agreement and kappa coefficients between qualitative evaluation of LVWM by AFI temporary criteria and qualitative evaluation of LVWM by experienced cardiologist 2 (0.784 and 0.479, respectively) were inferior to those comparing experienced cardiologists (0.845 and 0.595) but superior comparing experienced cardiologist with non-experienced resident (0.696 and 0.323), and between the 2 non-experienced-residents (0.682 and 0.347). CONCLUSION: Qualitative evaluation of LVWM using temporary AFI criteria had a 97% success rate and agreed well with findings of an experienced cardiologist. AFI can be a useful tool for training residents.

Collagen vitrigel scaffold for regenerative medicine of the trachea: experimental study and quantitative evaluation.

CONCLUSION: Our technique for tracheal regeneration using a collagen vitrigel scaffold affords a feasible approach for accelerating epithelial regeneration on the intraluminal surface of the host tracheal defect. OBJECTIVES: The purpose of the study was to quantitatively evaluate the effectiveness of a collagen vitrigel scaffold for the regeneration of the tracheal epithelium. METHODS: The collagen vitrigel scaffold was developed by conjugating a collagen vitrigel membrane to a collagen sponge to promote both epithelial cell growth and mesenchymal cell infiltration. The collagen vitrigel scaffold was implanted into tracheal defects in rats as the vitrigel model, and a conventional collagen sponge was implanted as a control model. The structure of the regenerated tissue was observed and thickness of the epithelium was quantitatively evaluated by histological examination. RESULTS: Histological findings showed the surface of the collagen vitrigel scaffold to be flat in comparison with that of the conventional collagen sponge. At 7, 14, and 28 days post-implantation, the average thickness of the regenerated epithelial layer in the vitrigel model group was greater than that in the control group.

Bioengineered prosthesis with allogenic heterotopic fibroblasts for cricoid regeneration.

OBJECTIVES/HYPOTHESIS: This study aimed to determine the effectiveness of a bioengineered prosthesis with allogenic heterotopic fibroblasts for cricoid regeneration. STUDY DESIGN: Experimental study using a rat model. METHODS: Bioengineered prosthetic grafts consisting of collagen sponge, polypropylene mesh, collagen gel, and allogenic dermal fibroblasts were implanted into rat cricoid defects. Control grafts were composed of collagen sponge and polypropylene mesh. Regenerated subglottic tissue was subsequently examined histologically. RESULTS: Epithelization and changes of collagen fibers occurred more rapidly in the bioengineered model than in the control model. Neogenetic cartilage was observed to form around the ends of cricoid cartilage in both models. CONCLUSIONS: Heterotopic fibroblasts appear to accelerate epithelial and subepithelial regeneration in a rat model.

Suitable solutions for reconstituting the ultrasound contrast agent "Levovist" used in contrast echocardiogram: in vitro and in vivo evaluation of the influence of osmotic pressure.

PURPOSE: To evaluate the influence of the osmotic pressure of solutions used for reconstituting the ultrasound contrast agent "Levovist" on the degree of video intensity of the enhancement and video intensity decay in contrast echocardiogram, we used 6 solutions with different osmotic pressures in both vitro and in vivo experiments. MATERIALS AND METHODS: In the in vitro experiments, Levovist was reconstituted with 6 kinds of solutions with different osmotic pressures (Lactate Ringer's solution, 2.5%, 5%, 7.5%, and 20% glucose and distilled water) and peak video intensities and video intensity decay were measured. In the in vivo experiments, contrast echocardiography was performed in 7 adult volunteers, following the intravenous injections of Levovist, previously reconstituted with one of 2 solutions (5% glucose or distilled water). RESULTS: In vitro, at peak time, Levovist reconstituted with either Lactate Ringer's solution, 2.5% glucose, 5% glucose, or distilled water had good peak video intensities. At 30 s after peak time, Levovist reconstituted with Lactate Ringer's solution had greater enhancement and less decay than the other 5 solutions (P<0.001). In vivo, at 180 heart beats after peak time, the video intensity decay with 5% glucose was greater than that with distilled water (150+/-13 dB, 123+/-25 dB, respectively, P<0.05). CONCLUSION: In this study, among various (2.5-20%) glucose solutions, the stability of the microbubbles differed, depending on the degree of osmotic pressure of the respective solutions; 5% glucose was the best. However, overall, the most suitable solution for reconstituting Levovist, was Lactate Ringer's solution. These findings could lead to effective strategies for better contrast echocardiography using Levovist by changing the current solution of choice to Lactate Ringer's solution or 5% glucose.