[AcrySof® Toric (SN60T) intraocular lens implantation: refractive predictibility and aberrometric impact of decentration]. / Prédictibilité réfractive et retentissement aberrométrique du décentrement des implantations toriques du pseudophaque de type SN60T-AcrySof®.

PURPOSE: To evaluate refractive outcomes of toric intraocular lens (IOL) implantation with a detailed analysis of decentration and its effect on aberrometry. METHODS: This retrospective study enrolled 19 eyes implanted with SN60T AcrySof(®) Toric (Alcon - USA) IOL's. Spherocylindric correction was studied in depth by the Alpins method, and retro-illumination images were used to analyze the alignment of the IOL with its intended axis. IOL decentration as well as its aberrometric impact were evaluated with a strict, novel protocol. RESULTS: Three months postoperatively, uncorrected distance visual acuity was greater or equal to 20/40 in 94.74% of cases, postoperative subjective cylinder was less or equal to 0.5 D in 68.42% of eyes, with a mean index of success of 0.24. Mean error of toric IOL alignment was 5.68° (0 to 14). Mean IOL decentration was 0.78 mm (0 to 1.78) with a mean coma and trefoil of 0.18 µ (0.06 to 0.33) and 0.19 µ (0.05 to 0.51), respectively. The larger the IOL decentration, the higher the optical aberrations were. CONCLUSION: Toric intraocular lens implantation is an effective, safe and predictable method of spherocylindrical correction during cataract surgery, with a refractive accuracy similar to that of LASIK in the treatment of astigmatism in young patients. IOL decentration produces optical aberrations including coma and trefoil, which interfere with visual performance.

Rigorous analysis of highly tunable cylindrical transverse magnetic mode re-entrant cavities.

Cylindrical re-entrant cavities are unique three-dimensional structures that resonate with their electric and magnetic fields in separate parts of the cavity. To further understand these devices, we undertake rigorous analysis of the properties of the resonance using "in-house" developed Finite Element Method (FEM) software capable of dealing with small gap structures of extreme aspect ratio. Comparisons between the FEM method and experiments are consistent and we illustrate where predictions using established lumped element models work well and where they are limited. With the aid of the modeling we design a highly tunable cavity that can be tuned from 2 GHz to 22 GHz just by inserting a post into a fixed dimensioned cylindrical cavity. We show this is possible, as the mode structure transforms from a re-entrant mode during the tuning process to a standard cylindrical transverse magnetic mode.

Millijoule laser pulse delivery for spark ignition through kagome hollow-core fiber.

We report on power handling oriented design of kagome lattice hollow-core fiber and demonstrate through it for the first time nanosecond laser pulses induced spark ignition in a friendly manner. Two different core designs and transmission bands are investigated and evaluated. The energy threshold damage was measured to be in excess of the 10 mJ level and the output power density is approaching the TW/cm2 after focusing; demonstrating the outstanding ability of such fiber for high power delivery.

Physical capability outcomes after total disc replacement with ProDisc-L.

BACKGROUND: Lumbar disc arthroplasty (total disc replacement [TDR]) outcomes have been evaluated using subjective, patient-reported measures of pain, health, and functional impairment. As a condition of TDR coverage, our institution's health plan required that objective physical performance data be collected. Thus our study was designed to explore (1) the feasibility of using preoperative and 1-year postoperative performance on functional capacity tasks as an outcome metric for TDR with ProDisc-L (PD-L) (Synthes Spine, West Chester, Pennsylvania), (2) the magnitude and significance of changes in preoperative and postoperative performance, and (3) whether changes noted in performance are reflected in the subjective measures. METHODS: Seven adapted WorkWell tasks (physical capability assessment tool [PCAT]) (WorkWell Systems, Duluth, Minnesota) were performed preoperatively and 1 year postoperatively by 18 patients who received either single-level or 2-level PD-L implants. Demographic and medical data were reviewed. RESULTS: The PCAT was implemented easily, and the tasks took approximately 30 minutes to complete. Percent improvement and preoperative and postoperative physical capability outcomes for each PCAT task are as follows: squat, 79% (10.7 ± 7.1 repetitions vs 19.2 ± 2.0 repetitions, P < .001); forward bend, 121% (110.2 ± 68.8 seconds vs 243.6 ± 77.2 seconds, P < .001); kneel, 92% (283.2 ± 173.2 seconds vs 544.7 ± 109.3 seconds, P < .001); floor-to-waist lift, 128% (16.1 ± 9.9 lb vs 36.7 ± 20.3 lb, P < .001); horizontal carry, 119% (19.7 ± 8.6 lb vs 43.2 ± 18.3 lb, P < .001); push, 32% (67.7 ± 19.2 lb vs 89.4 ± 24.4 lb, P < .001); and pull, 40% (57.6 ± 17.1 lb vs 80.9 ± 26.4 lb, P < .001). Visual analog scale scores for pain (5.1 ± 1.7 vs 1.4 ± 1.6, P < .001), Oswestry Disability Index scores (49.0% ± 13.2% vs 15.2% ± 14.3%, P < .001), and amount of narcotic use (26.1 ± 43.8 mg of morphine equivalent vs 1.9 ± 7.3 mg of morphine equivalent, P = .031) also improved. In single-level cases, comparison of L4-5 versus L5-S1 showed significant differences only with the forward bend task (P = .002). CONCLUSIONS/CLINICAL RELEVANCE: The physical capability outcome may be a feasible outcome metric. PD-L implantation may result in substantial improvements in physical performance. Similar benefits shown in a larger series over a longer timeframe could have important implications for the long-term health, productivity, and cost of health care for this patient population.

Prevention of vertebral body-splitting fractures after multilevel ProDisc-L implantation.

BACKGROUND: Prior studies of multilevel ProDisc-L (PD-L) implants (Synthes Spine, Inc., West Chester, Pennsylvania) using the standard US technique have used conventional radiography postoperatively. We found vertebral body-splitting fractures (VB-SFs) in interposed vertebral bodies after 5 sequential multilevel PD-L device implantations using the standard US technique. These were identified with postoperative computed tomography (CT) but were not visible on plain radiographs. In an additional patient, we found that a stress-relieving, pilot holes-only technique did not prevent VB-SFs. The 5 patients operated on with the standard technique composed the background series against which we compared the incidence of VB-SFs in patients operated on with a modification of the standard US technique-a combination of stress-relieving pilot holes, removal of cortex in the chisel path, and a fenestrated chisel (PH/CR/FC)-intended to reduce the incidence of VB-SFs in multilevel PD-L constructs. METHODS: Patients receiving multilevel PD-L implants at 2 sites-1 in the United States and the other in Germany-were operated on with the PH/CR/FC technique and their postoperative CT scans evaluated for the presence of VB-SFs. The frequency of VB-SFs in these patients was compared with that of the 5 patients from the background series who were operated on by the standard US technique. The groups' mean sex, age, body mass index, and vertebral body height, as well as average spinal T score, were also compared. RESULTS: No fractures were found in 13 interposed vertebral bodies in 11 patients operated on with the PH/CR/FC technique, as compared with 4 VB-SFs and 1 anterior keel cut-to-anterior keel cut fracture in 5 interposed vertebral bodies in 5 patients operated on with the US technique (P ≤ .001). Although the sample sizes were small, this difference in fracture rate was not associated with sex, age, body mass index, or average spinal T score. At up to 13 months of follow-up of patients in the background series, we found that VB-SFs tend not to bridge with bone, instead forming sclerotic margins. CONCLUSIONS: The PH/CR/FC technique studied reduced the incidence of VB-SF in multilevel PD-L implants. Because previously published multilevel studies did not use postoperative CT scans and because VB-SFs are not visible on conventional radiography, the incidence of VB-SFs in multilevel PD-L applications may be higher than previously reported. Our findings may contribute to prevention of complications in total disc replacement.

A new paradigm for staging pedicle screw-based spinal procedures: rationale, feasibility, safety, and efficacy.

OBJECT: The aims of this study were to present the rationale for and the evolution of a staged, two-procedure paradigm for spinal surgery requiring pedicle screw instrumentation, and to evaluate the feasibility, safety, and efficacy of the technique. METHODS: The rationale for the new algorithm is presented for consideration in the form of unproven hypotheses subject to verification by subsequent studies. The first stage of the two-staged algorithm, performed in an interventional radiology (IR) setting, involves percutaneous placement of either headless pedicle screws or K-wire fragment placeholders of the trajectory for pedicle screws. The second stage, performed days or weeks later, involves open surgical completion of instrumentation placement and other surgical objectives. The techniques for IR percutaneous K-wire fragment and percutaneous screw placement evolved over the duration of the study. Instrumentation was placed in 126 pedicles in 25 patients. Efficacy was equated to the accuracy of screw placement, which was evaluated using computed tomography (CT). Algorithms incorporating correction for metal artifact were developed to determine deviation of the screws and K-wire fragments from proper position. Over 1500 measurements were made to evaluate K-wire fragment and screw position in the 116 instrumented pedicles for which CT data were available. RESULTS: Accuracy of placement (relative to both cortical and pedicle breaches or to only pedicle breaches) was 98 to 100% for K-wire fragments, 96 to 98% for screws following K-wire fragments, and 100% for percutaneous screws. The only adverse consequence of pedicle screw placement by this method was one infection that occurred 8 months postoperatively. CONCLUSIONS: The staged, two-procedure paradigm for pedicle screw placement proved, within the limits of this study, to be feasible, safe, and effective; therefore, the unproven rationale behind the new paradigm merits further evaluation in a larger cohort of patients with randomized, matched controls.

An institutional approach to maintenance of excellent outcomes for carotid endarterectomy in a setting with moderate-to-low procedure volume.

BACKGROUND: Institutions and surgeons with high procedure volumes have been reported to have lower morbidity and mortality rates for patients undergoing carotid endarterectomy. Demonstrating comparable results is essential for centers with moderate or low volume. If comparable results cannot be demonstrated, a low- to moderate-volume center should not perform the procedure. STUDY DESIGN: A prospective study of a program to achieve and sustain excellent outcomes after carotid endarterectomy was conducted at a single institution with low-to-moderate volumes. Results of this effort from January 1997 through December 2005 are reported. Key features of our approach include institutional control over which and how many surgeons can perform carotid endarterectomy. Surgeons must be experienced carotid surgeons and consistently perform more than 12 procedures annually and be continuously monitored. Surgical outcomes were independently audited through a mandated institutional carotid endarterectomy data registry. Surgeons with poor outcomes are barred from doing carotid endarterectomies; and annually updated outcomes data are posted on the Internet. RESULTS: This approach was used for 555 carotid endarterectomies in 503 patients. Our outcomes-with total death and disabling stroke rate of 1.6%-compare favorably with, and are not statistically different from, published benchmarks, despite volumes at our institution ranging from 44 to 81 patients annually and the participation of 8 surgeons during the study period. CONCLUSIONS: Surgeons should perform carotid endarterectomies only if excellent outcomes can be demonstrated. We conclude that by using an approach like ours, even institutions with moderate-to-low carotid endarterectomy volumes can achieve excellent outcomes. We propose that all institutions should assume responsibility for ensuring excellent carotid endarterectomy outcomes using a comprehensive outcomes-based approach with independent auditing similar to that presented here.

Effect of approach side during anterior cervical discectomy and fusion on the incidence of recurrent laryngeal nerve injury.

OBJECT: This retrospective study was designed to determine whether side of approach during instrumented, one- or two-level primary anterior cervical discectomy and fusion (ACDF) affects the incidence of recurrent laryngeal nerve (RLN) injury diagnosed by observation of the vocal cords (OVC). METHODS: Records of all patients who underwent one- or two-level instrumented primary ACDF (418 patients) between January 1995 and February 2004 were reviewed. Data collected from these charts included surgeon, patient demographics, preoperative diagnosis, side of exposure, number of vertebral levels fused, and presence of RLN injury diagnosed by OVC after referral for persistent dysphonia. Time from surgery to OVC for patients with right-sided exposures was not statistically different from that for patients with left-sided exposures. Of 418 patients, 278 (66.5%) had right-sided exposures and 140 (33.5%) had left-sided exposures. Eight RLN injuries (1.9%) were noted-five in patients with right-sided exposures (1.8%) and three in patients with left-sided exposures (2.1%). The difference between right- and left-sided injury rates was shown to be nonsignificant using Fisher exact tests. CONCLUSIONS: Results indicate that, given the study's sample size, side of approach during instrumented, one- or two-level primary ACDF has no significant effect on RLN injury incidence in patients with persistent dysphonia referred for OVC. The definitive answer regarding the true incidence of RLN injury relative to approach side awaits a prospective study with preoperative, immediate postoperative, and periodic OVC in a large, homogeneous population with sufficient numbers of patients with right- and left-sided approaches.

Supercontinuum generation system for optical coherence tomography based on tapered photonic crystal fibre.

We report smooth and broad continuum generation using a compact femtosecond Ti:Sapphire laser as a pump source and a tapered photonic crystal fibre as a nonlinear element. Spectral output is optimized for use in optical coherence tomography, providing a maximum longitudinal resolution of 1.5 microm in free space at 809 nm centre wavelength without use of additional spectral filtering.

Extracellular protease activity of different Pseudomonas strains: dependence of proteolytic activity on culture conditions.

AIMS: This study investigated the effect of growth conditions on proteolytic activity of a Pseudomonas strain, named Pseudomonas sp. LBSA1, isolated from bulk raw milk. It was compared with three Pseudomonas chlororaphis and one Pseudomonas fluorescens strain from culture collections. METHODS AND RESULTS: Bacteriae were grown in a minimal salt medium. For all the strains, addition of 1% (v/v) skim milk to the growth medium was sufficient to induce protease production in 48-h culture. Addition of 1 mmol l(-1) calcium chloride permitted the detection of proteolytic activity of four strains in 48-h cultures but not for Pseudomonas sp. LBSA1. The five strains presented two patterns of proteolytic activity when grown in the minimal salt medium supplemented with 2% (v/v) skim milk at various temperatures for 48 h. Two electrophoretic protease patterns were also obtained from the zymogram of extracellular medium for the five strains. CONCLUSIONS: The growth conditions permitting protease production are variable and do not depend on the genus of the producing strain. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time a study on proteolytic activity of P. chlororaphis strains is reported. Among the tested criteria, zymograms of extracellular medium were the only ones that permitted distinguishing the P. chlororaphis strains from the P. fluorescens strain.

Characterization and proteolytic origins of specific peptides appearing during lipopolysaccharide experimental mastitis.

Based on the compositional change of the proteose peptone fraction, proteolysis was studied over time following lipopolysaccharide-induced experimental mastitis. Electrophoresis of the proteose peptone fraction revealed many degradation products. Five peptides were identified by amino-terminal sequencing as internal fragments of beta-, kappa-, alpha(s1)-, and alpha(s2)-casein that were generated by somatic cell proteases. Although kappa-casein is considered particularly resistant to endogenous proteolysis, a kappa-casein peptide was electrophoretically isolated in association with a beta-casein fragment. The in vitro kinetic studies of caseinate hydrolysis by elastase, one of the main polymorphonuclear neutrophil (PMN) proteases, suggested that the beta-casein peptide might be generated by elastase. In addition, elastase activity in milk PMN was higher during the inflammation of the mammary gland than prior to infusion.

Enzymatic assays for native plasmin, plasminogen and plasminogen activators in bovine milk.

Rapid and sensitive assays for plasmin, plasminogen and plasminogen activators (PA) were developed and applied to bovine milk. The reaction medium was clarified by addition of a dissolving agent after hydrolysis of a fluorescent substrate specific for plasmin. This final step enabled the use of larger sample amount with higher substrate concentration than other methods, and avoided previous sample preparation. The use of 4 g gelatin/l in buffers preserved plasmin activity, thus avoiding risks of overestimation of the assays results. Sensitivity, detection level, repeatability and analysis run time of plasmin and plasminogen assay were improved over previous enzymatic methods with synthetic substrates. The PA assay was assessed by measuring conversion of exogenous plasminogen into plasmin. A new kinetic approach was used to enable the direct determination of global PA activities on raw milk samples without interference from indigenous plasmin.

Viscoelastic properties of oil-water interfaces covered by bovine beta-casein tryptic peptides.

A combination of proteolysis and dilational rheology has been used to study the behavior of films of beta-casein (beta-CN) and of peptides spread at the oil-water interface. Identification of the peptides produced by trypsin hydrolysis of beta-CN in emulsion at 37 degrees C provided information on the structure of beta-CN adsorbed at the oil-water interface. Good interface properties were observed for beta-CN or its peptides, probably because of the amphipathic nature of beta-CN or a synergistic effect between hydrophilic and hydrophobic peptides. Remarkable surface activity was found for the amphipathic peptide beta-CN (f114-169). Rheological studies had shown that interface films made with peptide fractions or with beta-CN were elastic rather than viscous. Film made with the purified peptide beta-CN (f114-169) was merely elastic at the triolein-water interface. A decrease of the viscoelastic modulus was observed for aging beta-CN film but not for aging peptide films; The beta-CN decrease was related to the flexibility of its structure. When the interface is increased by the dilation of an aqueous droplet plunged into oil, beta-CN may expose new polypeptide trains to cover the increased interface, unlike peptides with simpler structures.

Camel (camelus dromedarius) milk PP3: evidence for an insertion in the amino-terminal sequence of the camel milk whey protein.

The camel (camelus dromedarius) milk proteose peptone 3 (PP3) was purified successively by size exclusion fast protein liquid chromatography and reversed phase high performance liquid chromatography and then characterized by amino acid residue composition determination and chemical microsequencing after CNBr or trypsin cleavages. In comparison with the previously reported structure of camel milk whey protein, the camel PP3 contains an insertion in the N-terminal region which has approximately 24 residues, whereas the remaining C-terminal regions of these two homologous proteins are essentially identical. The camel PP3 seems to contain a potential O-glycosylation site localized in this insertion and 2 or 3 phosphorylated serine residues. PP3 belongs to the glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1) family and could therefore play an immunological role in the camel or its suckling young.

[Regenerative potential in the organ of Corti after otic intoxication]. / Potentiel régénératif de l'organe de Corti après ototoxicité.

The auditory sensory cells are sensitive to a variety of influences such as noise, ototoxic drugs and aging. In the cochlea of mammals, the destroyed sensory cells are not replaced by new sensory cells. That leads to cochlear deafness, a frequent disease in human. Unfortunately, such auditory impairment is out of reach of treatment. The development of new therapeutic strategies in this field requires a precise knowledge of the mechanisms involved in auditory sensory cells disappearance and in organ of Corti's degeneration. The aim of our study was to characterize cellular and molecular changes in the cochlea of rats which had been intoxicated with the ototoxic antibiotic amikacin. The animals were sacrificed at different survival times during and after the antibiotic treatment and their cochleas were investigated using transmission and scanning electron microscopy and using confocal microscopy after tissue labellings with different fluorescent probes. The results revealed the existence of three periods. The first one corresponds to the disappearance of the sensory cells which die by apoptosis. During the second period, the organ of Corti undergoes a scarring process; concomitantly, a contingent of nonsensory supporting cells attempts to transdifferentiate directly into sensory cells. This process however fails, and the supporting cells never reach the status of hair cells. A general process of dedifferentiation of all the epithelial cells of the organ of Corti followed by a massive apoptosis of numerous epithelial cells and of most ganglion cells occurs during the third period. After that, the organ of Corti is definitely reduced to a simple monolayered epithelium. On the basis of these data, experimental strategies aimed i) to protect the sensory cells against apoptosis and ii) to promote sensory cell regeneration are now under study. They might have important implications in human therapy.

[Regenerative potential of the sensory epithelium of the mammalian organ of Corti after poisoning with ototoxic antibiotics]. / Potentiel régénératif de l'épithélium sensoriel de l'organe de corti du mammifère après intoxication aux antibiotiques ototoxiques.

Cochlear sensory hair cells are very sensitive to noxious influences such as ageing, noise and ototoxic drugs. Whereas lost auditory hair cells are replaced by new hair cells in the avian and lower vertebrates, cochlear sensory hair cells do not regenerate in mammals. Recently, we have observed transient atypical cells in the cochlea of amikacin intoxicated rats. We have related their presence to an attempt at sensory hair cell neodifferentiation. The aim of the present study was to i) investigate the mechanisms responsible for sensory hair cell losses during the intoxication and the subsequent appearance of atypical cells, ii) characterise the phenotype of these atypical cells and iii) evaluate the influence of cochlear immaturity in such an attempt at sensory hair cells neo-differentiation.

Sequential changes in anti-GAL-1 staining of the rat organ of Corti following amikacin exposure.

Hair cell loss and a non-functional epithelial reorganization appeared in the organ of Corti after acoustic or toxic damage. Moreover, in the drug damaged organ of Corti, transient atypical cells were recently described with characteristics of both immature hair cells and/or non-sensory epithelial cells. The phenotype of these atypical cells has been now investigated by using the galectine 1 (GAL-1) antibody. In the normal organ of Corti, this antibody recognizes all the epithelial cells except the sensory hair cells and their supporting cells. At PD 21, transient atypical cells were not stained by GAL-1 antibody, suggesting that they were originated from hair cells or their supporting cells. Later, the organ of Corti was substituted by an epithelial scare, GAL-1 stained. This study also emphasizes the particular resistance of the cochlear apex to degeneration after antibiotic intoxication.

Morphological and molecular changes in the inner hair cell region of the rat cochlea after amikacin treatment.

This study investigates the morphological and molecular changes that occur in the inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and PND16. Cochleae were examined at PND16 to PND120 using both scanning and transmission electron microscopy and molecular fluorescent labeling. The inner hair cells showed obvious signs of apoptosis in response to amikacin treatment and most of them were missing by one week after the end of the aminoglycoside exposure period. Concomitantly, the epithelium became scarred as the surrounding supporting cells expanded and filled the space vacated by the missing IHCs. The mid-basolateral region of these modified supporting cells was surrounded by many afferent and efferent terminals. However, these cells expressed neither calbindin nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated organ of Corti in the rat. In addition, these supporting cells remained attached to the basal lamina by a thin cytoplasmic process. The supporting cells surrounding the inner hair cells therefore appear unable to convert directly into inner hair cells following aminoglycoside induced hair-cell loss but may be able to provide trophic support for the remaining afferent and efferent neurites.

Attempt at hair cell neodifferentiation in developing and adult amikacin intoxicated rat cochleae.

Recent studies have shown that an attempt at auditory hair cell neodifferentiation occurs in vivo in the rat organ of Corti after amikacin intoxication during the last stages of cochlear maturation. Atypical cells, with morphological characteristics reminiscent of very immature sensory hair cells, were transiently observed after outer hair cell losses. The aim of the present study was to assess (i) if this attempt at hair cell neodifferentiation was related to the degree of maturity of the organ of Corti and (ii) to characterise morphological and molecular changes in the scarring epithelium. We therefore investigated, using electron and confocal microscopy, morphological and molecular changes in cochleae from rats treated with amikacin at two different periods: from post natal day (PND) 1 to PND 8, when the organ of Corti is very immature; and from PND 30 to 37, when the organ of Corti is morphologically and functionally mature. In both groups, transient atypical cells were observed, attesting that the attempt at hair cell neodifferentiation is not strictly related to the immaturity of the cochlea. The results also suggest that Deiters cells are involved in the appearance of atypical cells, possibly through a transdifferentiation process. Finally, it appears that non-sensory epithelial cells from the outer spiral sulcus progressively colonize the region of pre-existing outer hair cells.

Characterization of atypical cells in the juvenile rat organ of corti after aminoglycoside ototoxicity.

Hair cell regeneration is well documented in the inner ear sensory epithelia of lower vertebrates and birds and may occur in the vestibular organs of mammals. By contrast, hair cell loss in the mature mammalian cochlea is considered irreversible. However, recent reports have suggested that an attempt at hair cell regeneration could occur in vivo in aminoglycoside-lesioned cochleas from neonatal rats. After amikacin treatment, atypical cells with apical specialization reminiscent of early differentiating stereocilia are transiently present at the apex of the intoxicated cochleas but fail to differentiate as hair cells in later stages. In the present study, we used electronic microscopy, histochemistry, and confocal microscopy to investigate the cellular rearrangements in the amikacin-lesioned organ of Corti of rat pups. In addition, we used 5-bromo-2'-deoxyuridine immunocytochemistry to determine whether mitotic processes are involved in the formation of the atypical cells. The morphologic and molecular data suggest that atypical cells are not recovering hair cells, but share characteristics of immature hair cells and supporting cells. Proliferative cells were absent from the region occupied by atypical cells, suggesting that the latter did not arise through mitotic processes. Altogether, the present results support the hypothesis that atypical cells arise through direct transformation of some of the supporting cells that reorganize during hair cell degeneration.