Laryngeal Transplantation in 2005: A Review

There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.     

Effect of asymmetric vocal fold stiffness on traveling wave velocity in the canine larynx.

The vocal fold (VF) traveling wave is essential to normal voice production. The present investigation describes a new method to determine traveling wave velocity (TWV) in the in vivo canine phonatory model. This method synchronizes photoglottographic and electroglottographic waveforms with videostroboscopic images to determine the duration of time the traveling wave moves between two tattoos placed a known distance apart between the upper and lower margins of each VF. Using this method, we compared the TWV of a paralyzed VF with the TWV of the contralateral, electrically stimulated VF during phonation in two canines. In addition, the presumed VF stiffness asymmetry in the simulated acute recurrent laryngeal nerve paralysis state was confirmed by measuring Young's modulus of each VF. The results indicated that the TWV of the paralyzed VF averaged 55% of the TWV of the normal, stiffer VF when the glottal gap was small and entrainment occurred. This study demonstrated the feasibility of quantifying traveling wave motion in asymmetric VF stiffness disorders. The potential use of TWV in human beings as a target to optimize the phonosurgical results in asymmetric VF stiffness disorders is discussed.     

Resting metabolic rate and the influence of the pretesting environment.

We examined the effect of pretesting environment on measurement of resting metabolic rate (RMR). RMR was measured in 18 older (66.1 +/- 1.4 y) individuals after an overnight stay in the Clinical Research Center (ie, inpatient) and after subjects transported themselves to the laboratory (ie, outpatient). Similar measurements were also performed after an 8-wk endurance-training program. RMR was higher (P less than 0.01) before exercise training in subjects who transported themselves to the laboratory (ie, outpatients; 4.9 +/- 0.13 kJ/min) than in inpatients (4.6 +/- 0.13 kJ/min) and after exercise training in outpatients (5.4 +/- 0.08 kJ/min) vs inpatients (5.0 +/- 0.13 kJ/min). Training increased RMR under both inpatient (10%; P less than 0.01) and outpatient (11%; P less than 0.01) conditions. We conclude that RMR is higher when measured under outpatient conditions in older volunteers. Therefore, when daily energy requirements based on the assessment of RMR are being estimated, the pretesting environment should be considered. However, the exercise-training-induced increase in RMR can be detected by using either an inpatient or an outpatient protocol.     

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G- CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in- vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.      

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.