Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation.

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.

Evaluation of a commercial orthopaedic metal artefact reduction tool in radiation therapy of patients with head and neck cancer.

OBJECTIVE: To assess the image quality and dosimetric effects of the Philips orthopaedic metal artefact reduction (OMAR) (Philips Healthcare System, Cleveland, OH) function for reducing metal artefacts on CT images of head and neck (H&N) patients. METHODS: 11 patients and a custom-built phantom with metal bead inserts (alumina, titanium, zirconia and chrome) were scanned. The image was reconstructed in two ways: with and without OMAR (OMAR and non-OMAR image). The mean and standard deviation values of CT Hounsfield unit (HU) for selected regions of interest of each case were investigated for both images. Volumetric modulated arc therapy plans were generated for all cases. Gamma analysis of each dose distribution pair in the patient (1%/1 mm criteria) and phantom (2%/2 mm and 3%/3 mm criteria) images was performed. The film measurements in phantom for two metal beads were conducted for evaluating the calculated dose on both OMAR and non-OMAR images. RESULTS: In the OMAR images, noise values were generally reduced, and the mean HU became closer to the reference value (measured from patients without metal implants) in both patient and phantom cases. Although dosimetric difference was insignificant for the eight closed-mouth patients (γ = 99.4 ± 0.5%), there was a large discrepancy in dosimetric calculation between OMAR and non-OMAR images for the three opened-mouth patients (γ = 91.1%, 94.8% and 96.6%). Moreover, the calculated dose on the OMAR image is closer to the real delivered dose on a radiochromic film than was the dose from the non-OMAR image. CONCLUSION: The OMAR algorithm increases the accuracy of CT HU and reduces the noise such that the entire radiation treatment planning process can be improved, especially for contouring and segmentation. ADVANCES IN KNOWLEDGE: OMAR reconstruction is appropriate for the radiotherapy planning process of H&N patients, particularly of patients who use a bite block.

EFFECTS OF RESISTANCE EXERCISES AND COMPLEX DECONGESTIVE THERAPY ON ARM FUNCTION AND MUSCULAR STRENGTH IN BREAST CANCER RELATED LYMPHEDEMA.

The incorporation of resistance exercises into the lifestyle of patients with lymphedema is understudied and an emerging interest. We investigated the effectiveness and results of adding a moderate intensity resistance exercise program for 8 weeks in conjunction with intensive CDT for 1 or 2 weeks (depending on severity) on arm volume, arm function, QOL, and muscular strength in patients with breast cancer-related lymphedema. This prospective, pilot trial included forty-four patients with a history of breast cancer who were beginning complex decongestive therapy for lymphedema. They were assigned to either the intervention (n = 22) or control (n = 22). groups. The intervention comprised of resis- tance band exercises 5 times a week for 8 weeks. These were initially supervised during the intensive lymphedema treatment, but performed independently during the study period. Limb volume, muscular strength, and the European Organization for Research and Treatment of Cancer QOL Questionnaire C30 (EORTC QLQ-C30), EORTC-Breast Cancer-Specific QOL Questionnaire (EORTC QLQ-BR23), and Disabilities of Arm, Shoulder, and Hand (DASH) questionnaires were assessed at baseline and at 8 weeks. After 8 weeks, the intervention group demonstrated statistically significant differences (p < 0.05) in the DASH score and muscular strength compared to the control group. Our results indicate that upper body resistance exercise demonstrates a positive effect on arm function and muscular strength without increasing arm volume in breast cancer related lymphedema during and shortly post intensive CDT lymphedema treatment.

Congenital meniscoid articular disc of the triangular fibrocartilage complex.

We report the case of a 24-year-old man with a congenital meniscoid articular disc of the triangular fibrocartilage complex with extensor carpi ulnaris tenosynovitis. His young age, the normal articular cartilage, the lack of degenerative changes at the margins of the defect and its bilateral occurrence made this diagnosis likely. A congenital defect of the articular disc of the triangular fibrocartilage complex should not be misinterpreted as a traumatic rupture and is usually asymptomatic.

Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.

Sensorineural hearing loss associated with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene. In western populations, less than one-half of the affected individuals with EVA have two mutant SLC26A4 alleles, and EVA is frequently caused by unknown genetic or environmental factors alone or in combination with a single SLC26A4 mutation as part of a complex trait. In this study, we ascertained 26 Korean probands with EVA and performed nucleotide sequence analysis to detect SLC26A4 mutations. All subjects had bilateral EVA, and 20 of 26 were sporadic (simplex) cases. Fourteen different mutations were identified, including nine novel mutations. Five mutations were recurrent and accounted for 80% of all mutant alleles, providing a basis for the design and interpretation of cost-efficient mutation detection algorithms. Two mutant alleles were identified in 21 (81%), one mutant allele was detected in three (11%), and zero mutant allele was detected in two (8%) of 26 probands. The high proportion of Korean probands with two SLC26A4 mutations may reflect a reduced frequency of other genetic or environmental factors causing EVA in comparison to western populations.

Expression of phospholipase C-gamma1 in experimental cholesteatoma using Mongolian gerbils.

Phospholipase C (PLC)-gamma1 is known to play a central role in ligand-mediated signal transduction for cell proliferation. The purpose of this study was to elucidate the distribution of PLC-gamma1 in deep meatal skin, retroauricular skin and cholesteatoma matrix of experimental animals. We induced canal ligation cholesteatoma using Mongolian gerbils and investigated the expression of PLC-gamma1 in this model by using Western blot analysis and immunohistochemistry. By Western blot analysis, considerably higher levels of PLC-gamma1 protein were detectable in experimental cholesteatoma. On immunohistochemistry, experimental cholesteatoma showed more intense immunolabeling of PLC-gamma1 protein than deep meatal skin and retroauricular skin. In conclusion, overexpression of PLC-gamma1 may in part contribute to abnormal proliferation and differentiation of experimental cholesteatoma in Mongolian gerbils.

Immunohistochemical study on proliferative activity of experimental cholesteatoma.

In this study, we induced canal ligation cholesteatoma using Mongolian gerbils and investigated the hyperproliferative nature of canal ligation cholesteatoma by using an immunohistochemical technique with proliferation markers (cytokeratin 13/16, PCNA, EGFR, thrombomodulin). Canal ligation cholesteatoma using Mongolian gerbils had a hyperproliferative character in the suprabasal cell layer similar to human cholesteatomas. This result will provide a good morphological basis for future cholesteatoma animal research concerning the pathogenesis of cholesteatoma.

Connexin26 mutations associated with nonsyndromic hearing loss.

OBJECTIVE: Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG mutation is the most frequent type of mutation in white populations. However, several other forms were reported, such as 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin26 (Cx26) found in patients with nonsyndromic hearing loss (NSHL) and newborns in the Korean population. STUDY DESIGN: The sequencing data for 147 unrelated patients with congenital NSHL and 100 audiologically screened newborns were included in this prospective study. METHODS: Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx26 mutations. RESULTS: Thirteen different types of mutations were found in the patients and newborns. V27I and E114G are the popular types of polymorphic mutations in both groups. 235delC-deletion and frameshift--was detected in patients (15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations--S85P, K41R, S72C, V84A, 176-191del, and 299-300del-were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiological evaluation of hearing threshold. CONCLUSION: The frequency of 235delC allele showed much higher in the patients (5%) than in newborns (0.5%). We rarely found 35delC mutant in both groups. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL according to ethnic background.

Epithelial differentiation in developing murine eustachian tube and middle ear.

Detailed information on how an epithelial differentiation occurred in the developing eustachian tube and middle ear would be helpful in understanding both normal physiology and pathology of the tubotympanum. This study was undertaken to establish patterns of laminin and E-cadherin in the embryonic mouse eustachian tube and middle ear by use of immunohistochemistry at a stage when epithelial differentiation is taking place. This study was also designed to clarify the role of the middle ear mesenchyme. During the development of the eustachian tube, relatively high immunoreactivity to laminin was observed in the epithelium at gestational days 16 and 17, when the developments of ciliated and secretory cells were first observed. At the time of birth, in contrast to epithelium of the eustachian tube, epithelium of the middle ear cavity showed predominant expression of laminin and E-cadherin. These findings suggest that the expressions of laminin and E-cadherin may be correlated with maturation of the epithelium in the eustachian tube and middle ear and that the epithelial differentiation of the developing murine eustachian tube and middle ear may be controlled by epithelial-mesenchymal interaction and cell-to-cell interaction.

Cell biology of tubotympanum in relation to pathogenesis of otitis media - a review.

The sterility of the eustachian tube and tympanic cavity of normal individuals is maintained not only by the adaptive immune system, but also by the mucociliary system and the antimicrobial molecules of innate immunity. Mucin production and periciliary fluid homeostasis are essential for normal mucociliary function and dysfunction of this system is an important risk factor for otitis media. The secreted antimicrobial molecules of the tubotympanum include lysozyme, lactoferrin, beta defensins, and the surfactant proteins A and D (SP-A, SP-D). Defects in the expression or regulation of these molecules may also be the major risk factor for otitis media.

Signal transduction pathway in human middle ear cholesteatoma.

Phospholipase C-gamma1 plays a central role in signal transduction, and it is important in cellular growth, differentiation, and proliferation. Human cholesteatoma in the middle ear is characterized by the presence of a keratinizing epithelium that is believed to have hyperproliferative properties. The purpose of this study is to elucidate the distribution of phospholipase C-gamma1 in cholesteatoma matrix and deep meatal skin with Western blot analysis and immunohistochemistry. In conclusion, overexpression of phospholipase C-gamma1 in cholesteatoma matrix suggests a possible derangement of enhanced growth signal transduction in keratinocytes.

Immunohistochemical study of cell proliferation using BrdU labelling on tympanic membrane, external auditory canal and induced cholesteatoma in Mongolian gerbils.

The Mongolian gerbil is a well-known animal model for induction of aural cholesteatomas. This animal model is useful for studying changes in the keratinizing epithelium. It is not known whether keratin accumulation can increase the proliferative activity of the keratinizing epithelium in tympanic membrane and meatal skin. In this study, we investigated the proliferative activity of the epidermis in induced aural cholesteatoma at various stages and in different areas of the tympanic membrane and meatal skin in normal gerbils. Anti-5-bromo-2- deoxyuridine (BrdU) was injected intraperitoneally to detect the proliferative activity of keratinizing epithelium. Immunohistochemistry with monoclonal BrdU antibody in the normal gerbil showed intense immunolabelled keratinocytes at the handle of malleus, and the superior parts of pars tensa and pars flaccida. Also, mitotic activity in the deep meatal skin was more active than in the lateral meatal skin. The induced aural cholesteatoma showed more active proliferation centre of the epithelial cell than eardrum and external ear canal of the normal gerbil. These observations suggest that the accumulation of the keratin debris might induce changes of the cellular proliferation in the external auditory meatus.

Laryngeal pacemaker using a temperature sensor in the canine.

With the use of a temperature sensor that would detect temperature changes during the respiratory cycle in the pharynx, electrical stimulation of the posterior cricoarytenoid muscle was achieved in dogs whose recurrent laryngeal nerves were artificially paralyzed. Due to the temperature difference between inspiratory and expiratory air flow, a trigger pulse was generated at the beginning of inspiration. The stimulation pulse following the trigger pulse stimulated the electrodes inserted into the posterior cricoarytenoid muscles. In all five canines, obvious abduction of the vocal folds synchronized with inspiration was observed during electrical pacing.