The effect of a bundle intervention for ambulatory otorhinolaryngology procedures on same-day case cancellation rate and associated costs.

Cancellations within 24 h of planned elective surgical procedures reduce operating theatre efficiency, add unnecessary costs and negatively affect patient experience. We implemented a bundle intervention that aimed to reduce same-day case cancellations. This consisted of communication tools to improve patient engagement and new screening instruments (automated estimation of ASA physical status and case cancellation risk score plus four screening questions) to identify patients in advance (ideally before case booking) who needed comprehensive pre-operative risk stratification. We studied patients scheduled for ambulatory surgery with the otorhinolaryngology service at a single centre from April 2021 to December 2022. Multivariable logistic regression and interrupted time-series analyses were used to analyse the effects of this intervention on case cancellations within 24 h and costs. We analysed 1548 consecutive scheduled cases. Cancellation within 24 h occurred in 114 of 929 (12.3%) cases pre-intervention and 52 of 619 (8.4%) cases post-intervention. The cancellation rate decreased by 2.7% (95%CI 1.6-3.7%, p < 0.01) during the first month, followed by a monthly decrease of 0.2% (95%CI 0.1-0.4%, p < 0.01). This resulted in an estimated $150,200 (£118,755; €138,370) or 35.3% cost saving (p < 0.01). Median (IQR [range]) number of days between case scheduling and day of surgery decreased from 34 (21-61 [0-288]) pre-intervention to 31 (20-51 [1-250]) post-intervention (p < 0.01). Patient engagement via the electronic health record patient portal or text messaging increased from 75.9% at baseline to 90.8% (p < 0.01) post-intervention. The primary reason for case cancellation was patients' missed appointment on the day of surgery, which decreased from 7.2% pre-intervention to 4.5% post-intervention (p = 0.03). An anaesthetist-driven, clinical informatics-based bundle intervention decreases same-day case cancellation rate and associated costs in patients scheduled for ambulatory otorhinolaryngology surgery.

Randomized clinical trial investigating the stress response from two different methods of analgesia after laparoscopic colorectal surgery.

BACKGROUND: One of the key elements of managed recovery is thought to be suppression of the neuroendocrine response using regional analgesics. This may be superfluous in laparoscopic colorectal surgery with small wounds. This trial assessed the effects of spinal analgesia versus intravenous patient-controlled analgesia (PCA) on neuroendocrine responses in that setting. METHODS: A randomized clinical trial was conducted with participation of patients undergoing laparoscopic colorectal surgery within a managed recovery programme. Consenting patients were allocated randomly to spinal analgesia or morphine PCA as primary postoperative analgesia. The primary outcome was interleukin (IL) 6 levels; secondary outcomes were levels of cortisol, glucose, insulin and other cytokines, pain scores, morphine use and length of hospital stay. Stress response analysis was conducted before operation, and 3, 6, 12, 24 and 48 h after surgery. RESULTS: Of 143 eligible patients, 133 were randomized and 120 completed the study. Baseline patient characteristics were similar in the two groups. There were no significant differences in median levels of insulin, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon γ, tumour necrosis factor α or vascular endothelial growth factor between the spinal analgesia and PCA groups at any time point. Three hours after surgery (but at no other time point) median (i.q.r.) levels of cortisol (468 (329-678) versus 701 (429-820) nmol/l; P = 0.004) and glucose (6.1 (5.4-7.5) versus 7.0 (6.0-7.7) mmol/l; P = 0.012) were lower in the spinal analgesia group than in the PCA group. Median (i.q.r.) levels of total intravenous morphine were lower in the spinal analgesia group (10.0 (3.3-15.8) versus 45.5 (34.0-60.5) mg; P < 0.001). CONCLUSION: Spinal analgesia reduced early neuroendocrine responses and overall parenteral morphine use. REGISTRATION NUMBER: NCT01128088 (http://www.clinicaltrials.gov).

Bioinformatics in otolaryngology research. Part two: other high-throughput platforms in genomics and epigenetics.

OBJECTIVES: This second segment of the two-part review summarises several modern high-throughput methods in genomics, epigenetics and molecular biology. Many principles from nucleotide sequencing and transcriptomics can be applied to other high-throughput molecular biology techniques. Specifically, this manuscript reviews: array comparative genome hybridisation; single nucleotide polymorphism arrays; microarray technology, used to study epigenetics; and methodology applied in proteomics. Finally, the review describes current methods for the integration of multiple molecular biology platforms. CONCLUSION: Progress in treating human disease in general will require close collaboration with experts in bioinformatics. Improved understanding, by clinicians and physician-scientists in our field, of the concepts presented in both parts of this review will advance diagnosis and therapy for diseases of the head and neck.

Bioinformatics in otolaryngology research. Part one: concepts in DNA sequencing and gene expression analysis.

BACKGROUND: Advances in high-throughput molecular biology, genomics and epigenetics, coupled with exponential increases in computing power and data storage, have led to a new era in biological research and information. Bioinformatics, the discipline devoted to storing, analysing and interpreting large volumes of biological data, has become a crucial component of modern biomedical research. Research in otolaryngology has evolved along with these advances. OBJECTIVES: This review highlights several modern high-throughput research methods, and focuses on the bioinformatics principles necessary to carry out such studies. Several examples from recent literature pertinent to otolaryngology are provided. The review is divided into two parts; this first part discusses the bioinformatics approaches applied in nucleotide sequencing and gene expression analysis. CONCLUSION: This paper demonstrates how high-throughput nucleotide sequencing and transcriptomics are changing biology and medicine, and describes how these changes are affecting otorhinolaryngology. Sound bioinformatics approaches are required to obtain useful information from the vast new sources of data.

Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival.

AIM: Multicentre randomized trials have demonstrated equivalent long-term outcomes for open and laparoscopic resection of colon cancer. Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection. Patients who receive adjuvant chemotherapy in < 8 weeks following surgery can have an improved survival. METHOD: Data were collated for patients having an elective laparoscopic or open resection for non-metastatic colorectal cancer between October 2003 and December 2010 and subsequently having adjuvant chemotherapy. Survival analysis was conducted. RESULTS: In all, 209 patients received adjuvant chemotherapy following open (n = 76) or laparoscopic (n = 133) surgery. Median length of stay was 3 days with laparoscopic resection and 6 days with open resection (P < 0.0005). Median number of days to initiation of adjuvant chemotherapy was 52 with laparoscopic resection and 58 with open resection (P = 0.008). The 5-year overall survival was 89.6% in patients receiving chemotherapy in < 8 weeks after surgery, compared with 73.5% who started the treatment over 8 weeks (P = 0.016). The 5-year overall survival for those patients with a laparoscopic resection was 82.3% compared with 80.3% with an open resection (P = 0.049). CONCLUSION: There is an overall survival advantage when patients receive adjuvant chemotherapy < 8 weeks after surgery. Laparoscopic resection allows earlier discharge and, subsequently, earlier initiation of adjuvant chemotherapy.

Increase in phosphorus losses from grassland in response to Olsen-P accumulation.

The Olsen-P status of grazed grassland (Lolium perenne L.) swards in Northern Ireland was increased over a 5-yr period (March 2000 to February 2005) by applying different rates of P fertilizer (0, 10, 20, 40, or 80 kg P ha(-1) yr(-1)) to assess the relationship between soil P status and P losses in land drainage water and overland flow. Plots (0.2 ha) were hydrologically isolated and artificially drained to v-notch weirs, with flow proportional monitoring of drainage water and overland flow. Annually, the collectors for overland flow intercepted between 11 and 35% of the surplus rainfall. Single flow events accounted for up to 52% of the annual dissolved reactive phosphorus (DRP) load. The Olsen-P status of the soil influenced DRP and total phosphorus (TP) concentrations in land drainage water and overland flow. Annual TP loss was highly variable and ranged from 0.19 to 1.55 kg P ha(-1) yr(-1) for the plot receiving no P fertilizer and from 0.35 to 2.94 kg P ha(-1) yr(-1) for the plot receiving 80 kg P ha(-1) yr(-1). Despite the Olsen-P status in the soils ranging from 22 to 99 mg P kg(-1), after 5 yr of fertilizer P applications it was difficult to identify a clear Olsen-P concentration at which P losses increased. Any relationship was confounded by annual variability of hydrologic events and flows and by hydrologic differences between plots. Withholding P fertilizer for over 5 yr was not long enough to lower P losses or to have an adverse effect on herbage P concentrations.

Gene expression profiles in HPV-infected head and neck cancer.

Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of head and neck squamous cell carcinoma (HNSCC). To evaluate the molecular pathogenesis of HPV-infected HNSCC, we compared gene expression patterns between HPV-positive and -negative HNSCC tumours using cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed HNSCC patients from an inner-city area of New York. Total DNA and RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference RNA standard using a 27 323 cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary HNSCC with a false discovery rate < 0.2. Focusing on never-smokers, we further identified a distinct subset of 123 genes that were specifically dysregulated in HPV16-positive HNSCC. Overexpressed genes in HPV-positive HNSCC tumours included the retinoblastoma-binding protein (p18), replication factor-C gene, and an E2F-dimerization partner transcription factor (TFDP2) that have also been found to be overexpressed in cervical cancer. An additional subset of genes involved in viral defence and immune response, including interleukins and interferon-induced proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced HNSCC.

Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray.

Our group has initiated experiments to epigenetically profile CpG island hypermethylation in genomic DNA from tissue specimens of head and neck squamous cell carcinoma (HNSCC) using a microarray of 12,288 CpG island clones. Our technique, known as a methylation-specific restriction enzyme (MSRE) analysis, is a variation of the differential methylation hybridization (DMH) technique, in that it is not an array comparison of two DNA samples using methylation-specific restriction enzymes. Instead, it is a comparison of a single DNA sample's response to a methylation-sensitive restriction enzyme (HpaII) and its corresponding methylation-insensitive isoschizomer (MspI). Estimation of the reproducibility of this microarray assay by intraclass correlation (ICC) demonstrated that in four replicate experiments for three tumor specimens, the ICC observed for a given tumor specimen ranged from 0.68 to 0.85 without filtering of data. Repeated assays achieved 87% concordance or greater for all tumors after filtering of array data by fluorescence intensity. We utilized hierarchical clustering on a population of 37 HNSCC samples to cluster tumor samples with similar DNA methylation profiles. Supervised learning techniques are now being utilized to allow us to identify associations between specific epigenetic signatures and clinical parameters. Such techniques will allow us to identify select groups of CpG island loci that could be used as epigenetic markers for both diagnosis and prognosis in HNSCC.

Halting the upward trend in soluble phosphorus transported from a grassland catchment.

An upward trend in soluble reactive phosphorus (SRP) concentrations in Northern Ireland rivers leading to increased eutrophication has been reported for the last two decades. To identify if a similar trend could be observed in land drainage waters SRP and other P fractions were measured weekly from 1989 to 1997 in land drainage from a 9-ha grassland catchment in Northern Ireland that had a mean P surplus applied of 23.4 kg P ha(-1) yr(-1). Regressions of annual median concentrations of P fractions in land drainage waters against time for 1989 through to 1997 showed significant increases of SRP and soluble unreactive phosphorus (SUP) of 2.4 and 1.2 microg P L(-1) yr(-1), respectively. However, the annual flow-weighted concentrations and loads of all P fractions did not show significant increases with time. During the period 1998-2000 a change of management was introduced when only maintenance dressings of P were applied to the catchment according to Ministry of Agriculture, Fisheries and Food guidelines. This resulted in significant reductions in SRP concentrations in 2000 compared with 1997.

Assessing the effectiveness of regulatory controls on farm pollution using chemical and biological indices of water quality and pollution statistics.

Water quality was measured in 42 streams in the Colebrooke and Upper Bann catchments in Northern Ireland over the period 1990-1998. Despite ongoing pollution control measures, biological water quality, as determined by the invertebrate average score per taxon (ASPT) index, did not improve and there was no appreciable decline in recorded farm pollution incidents. However, the lack of decline in pollution incidents could reflect changes in detection policy, as a greater proportion of incidents were recorded from less polluting discharges such as farm-yard runoff. In contrast, there was an improvement during 1997 and 1998 in annual chemical water quality classification based on exceedence values (90th percentiles) for dissolved oxygen, ammonium and BOD concentrations. In 1998, 11.9% of streams were severely polluted compared to 26.2% in 1990, while the proportion classed as of salmonid water quality, increased from 40.5% in 1990 to 59.6% in 1998. Although water quality in 1996 did not improve relative to 1990 values, there was a notable increasing trend from 1990 in the numbers of samples taken during the summer which had good water quality with low ammonium (<0.6mgN l(-1)) and high dissolved oxygen (> 70% sat). The trend for samples with low BOD (<4 mgl(-1)) was more erratic, but an improvement was apparent from 1994. These improvements in chemical water quality suggest that point-source farm pollution declined after 1990. The fact that this was not reflected in stream biology may reflect the limited time scale for biological recovery. An important factor preventing biological recovery may be the high pollution capacity of manures and silage effluent, so that even reduced numbers of farm pollution incidents can severely perturb stream ecosystems. The intractable nature of farm pollution suggests that there is a need to consider an interactive approach to problem resolution involving both farmers and regulators.

Changes in soil organic carbon storage under grassland as evidenced by changes in sulphur input-output budgets.

Information about temporal changes in soil organic carbon (C) pools may be obtained indirectly from changes in input-output budgets of organically combined nutrients such as sulphur (S). Sulphur budgets were therefore evaluated for Northern Ireland (NI) for the period 1940-1990, inclusive. These budgets indicated that the land or soil had acted first as a sink but then as a source for S, and that reserves of soil S built up between 1940 and 1965 were totally depleted by the mid-1980s. Pooled data from six long-term soil-monitoring sites on undisturbed grassland suggested that negative S budgets from the late-1970s onwards had been due to the net mineralization of soil organic matter and thus were indicative of net losses of organic C from surface soil horizons. There was some evidence that the decline in rainfall and fertiliser S inputs from the mid-1960s may have precipitated the breakdown of soil organic matter.

Stage 4 squamous cell carcinoma of the tongue in a child: complete response to chemoradiotherapy.

This report describes a complete response to a chemoradiotherapy regimen in a child with an advanced and unresectable squamous cell carcinoma of the tongue. An 8-year-old girl had stage 4 squamous cell carcinoma of the tongue (T4N2M0), causing severe trismus and dysphagia. She received hyperfractionated external beam radiotherapy (total 74.4 Gy) and concomitant intravenous infusion of hydroxyurea (0.313 mg/m2 per min) for 43 days. Grade 3 mucositis and myelosuppression were the main toxicities. There was marked symptomatic improvement, and the patient achieved a complete response. She is disease-free 24 months after treatment, and all the acute symptoms have resolved. The regimen was well tolerated with acceptable toxicity and led to a complete objective response. This regimen needs further evaluation to confirm its efficacy and to ascertain its long-term effects in children.

Workforce issues for the academic otolaryngologist.

BACKGROUND: The current medico-economic environment has led to profound changes in our health care system and questions of physician surplus. These issues have particularly affected the academic health care system, as research funding and departmental support have decreased, and many young otolaryngologists are questioning academic careers because of these uncertainties. The current study was undertaken to assess the workforce environment for the academic otolaryngologist, particularly the young physician. METHODS: Surveys were sent to the academic chairmen of all accredited otolaryngology residency programs in the United States, requesting information on faculty appointments--actual and projected-as well as subspecialty appointments and expectations of young faculty. RESULTS: The response rate was 60% (59/98). Faculty additions have been relatively stable from 1994 to 1998, with approximately 37 assistant professor and 5 associate professor positions filled yearly. Faculty additions were the result of departmental expansion in 83% of cases and spanned many subspecialties. The subspecialty positions most frequently added from 1994 to 1998 were generalists (57), head and neck oncologists (53), pediatric otolaryngologists (48), and otologists (39), with generalists filling 15 positions in 1998. Ninety-three percent of programs anticipate faculty additions in the next 5 years; most will be at the assistant professor level (77%), with 30% of positions for generalists, 20% for head and neck oncologists, and 18% for pediatric otolaryngologists. Faculty expectations are primarily clinical, with research being least important. CONCLUSIONS: Academic positions are available for the young otolaryngologist, particularly in the fields of general otolaryngology, head and neck oncology, and pediatric otolaryngology.

The workforce in otolaryngology-head and neck surgery: moving into the next millennium.

OBJECTIVE: The goal was to examine the current scope of otolaryngologists' practices, their geographic distribution, and the roles otolaryngologists and other specialists play in caring for patients with otolaryngic and related conditions of the head and neck. STUDY DESIGN: A large national survey and administrative claims databases were examined to develop practice profiles and compile a physician supply for otolaryngology. A focus group of otolaryngologists provided information to model future scenarios. RESULTS: The current and predicted workforce supply and demographics are at a satisfactory level and are decreasing as a proportion of the increasing population. Empiric data analysis supports the diverse nature of an otolaryngologist's practice and the unique role for otolaryngologists that is not shared by many other providers. Together with the focus group results, the study points to areas for which more background and training are warranted. CONCLUSIONS: This study represents a first step in a process to form coherent workforce recommendations for the field of otolaryngology.

Surgical treatment of the neck in cancer of the larynx.

Current concepts in management of the clinically negative and clinically positive neck in laryngeal cancer are reviewed. Occult disease in the neck not detected by physical and radiographic examination may also be difficult to identify on routine histologic examination. Immunohistochemistry or molecular analysis may detect metastatic involvement not apparent by light microscopy. The surgeon should be aware of the relatively high incidence of micrometastases in patients with laryngeal cancer to establish optimal treatment approaches. Elective treatment of the neck is recommended for supraglottic tumors staged T2 or higher, and glottic or subglottic tumors staged T3 or higher. The neck may be treated electively by either surgery or irradiation, but irradiation is best reserved for cases where that modality is employed for the primary tumor. Elective neck dissection provides important information for prognostic purposes and therapeutic decisions, by establishing the presence, number, location and nature of occult lymph node metastases. The selective lateral neck dissection (levels II, III and IV), unilateral or bilateral, is the procedure of choice for elective treatment. Paratracheal nodes (level VI) should be dissected in cases of advanced glottic and subglottic cancer. Complete radical or functional neck dissections are excessive in extent, as levels I and V are almost never involved. Sentinel lymph node biopsy may fail to detect tumor on frozen section examination or may not reveal 'skip' metastases. The clinically involved neck is usually treated by complete radical or functional neck dissection of levels I through V. Selective neck dissection has been employed successfully in selected cases, particularly for N1 or occasionally N2 nodal involvement. The selective neck dissection can be extended to include structures at risk. More advanced disease has been treated in this manner often in association with adjuvant chemotherapy and/or irradiation. While the benefit of adjuvant treatment is difficult to assess, it appears most useful in cases with extranodal spread of disease, a factor associated with the worst prognosis.

A spatial study of denitrification potential of sediments in Belfast and Strangford Loughs and its significance.

The C2H2 inhibition technique was employed to study seasonal denitrification potential rates in sediment slurries from tidal and subtidal sites in Belfast and Strangford Loughs, Northern Ireland. A comparison of denitrification rates obtained from this method with those obtained from the 15N-gas flux method generally showed good agreement. Depth profiles measured up to 1 m showed that denitrification decreased with depth, with highest values in the 0-5-cm fraction. For the Belfast Lough tidal system a multiple regression model was developed which explained 83% of the variation in denitrification potential. The independent variables were water content, sediment temperature, total oxidizable N in porewater and total organic N. The highest rate of denitrification potential, 2100 micromol N m(-2) h(-1), was found in areas where there was a high anthropogenic input of nutrients. Denitrification in sediments in both loughs can play a potentially significant role in removal of NO3- from the overlying water. In Belfast Lough the overall denitrification potential rate matched the external NO3-N inputs, whilst in Strangford Lough it exceeded it by sixfold, which suggests a potential to remove future additional anthropogenic inputs to the Lough.

Long-term swallowing problems after organ preservation therapy with concomitant radiation therapy and intravenous hydroxyurea: initial results.

OBJECTIVE: To evaluate the long-term effects on swallowing function of concomitant continuous infusion hydroxyurea and hyperfractionated radiation therapy used to treat advanced head and neck carcinoma. DESIGN: A prospective evaluation of swallowing function was performed on an inception cohort by analyzing posttreatment videoflouroscopic swallow function studies using radiological descriptors for pharyngeal transport abnormalities and temporal measures of structural movements, as well as by conducting patient interviews to assess alimentation, more than 1 year after tumor treatment (range, 52-124 weeks; median, 70 weeks). SETTING: Academic tertiary care referral medical center. PATIENTS: Ten patients, aged 44 to 71 years, with stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx. MAIN OUTCOME MEASURE: Radiographic and temporal swallow abnormalities, as well as functional status, were documented and compared with published norms and results of earlier swallowing studies when possible. RESULTS: Pharyngeal transport dysfunction and anterior segment abnormalities, manifested by epiglottic dysmotility, vallecular residue, laryngeal penetration, or aspiration, were evident in all 10 patients. Posterior segment abnormalities, such as pharyngeal stasis, constrictor dysmotility and piriform residue were documented in 8 patients. Three patients developed late aspiration, and the majority of patients showed persistent or worsened delay in laryngeal movement compared with their earlier posttreatment evaluations. Also, 3 patients developed a hypopharyngeal stricture, and 6 patients continued to require gastrostomy tube supplementation beyond 1 year. There was no association between site of primary, duration to swallowing evaluation, and severity of dysfunction. CONCLUSION: Prolonged and debilitating functional swallowing abnormalities may occur after this aggressive concomitant chemotherapy and radiotherapy regimen.

Early wound complications in advanced head and neck cancer treated with surgery and Ir 192 brachytherapy.

OBJECTIVES: Brachytherapy, either as primary or adjuvant therapy, is increasingly used to treat head and neck cancer. Reports of complications from the use of brachytherapy as adjuvant therapy to surgical excision have been limited and primarily follow Iodine 125 (I125) therapy. Early complications include wound breakdown, infection, flap failure, and sepsis, and late complications may include osteoradionecrosis, bone marrow suppression, or carotid injuries. The authors sought to identify the early wound complications that follow adjuvant interstitial brachytherapy with iridium 192 (IrS92). STUDY DESIGN: A retrospective chart review of all patients receiving adjuvant brachytherapy at a tertiary medical center over a 4-year period. METHODS: Nine patients receiving Ir192 brachytherapy via afterloading catheters placed during surgical resection for close or microscopically positive margin control were evaluated. It was used during primary therapy in six patients and at salvage surgery in three. Early complications were defined as those occurring within 6 weeks of surgical therapy. RESULTS: The overall complication rate was 55% (5/9), and included significant wound breakdown in two patients, minor wound dehiscence in three, and wound infection, bacteremia, and local tissue erosion in one patient each. All complications occurred in patients receiving flap reconstruction and one patient required further surgery to manage the complication. Complication rates were not associated with patient age, site, prior radiotherapy, timing of therapy, number of catheters, or dosimetry. CONCLUSIONS: The relatively high complication rate is acceptable, given the minor nature of most and the potential benefit of radiotherapy. Further study should be undertaken to identify those patients who will achieve maximum therapeutic benefit without prohibitive local complications.

Reversible sensorineural hearing loss following administration of muromonab-CD3 (OKT3) for cadaveric renal transplant immunosuppression.

This prospective study is a follow-up to a case report noting reversible sensorineural hearing loss after administration of OKT3 for immunosuppression in a steroid-resistant renal cadaveric transplant patient who was rejecting his transplant. The objective is to determine the interval estimate for incidence of sensorineural hearing loss following treatment with OKT3. Seven patients were admitted to the Renal Transplant Service at Montefiore Medical Center from July 1996 to July 1997 with steroid-resistant rejection of renal cadaveric transplants and received OKT3 as an immunosuppressant. All 7 patients received 3 audiograms: the first, prior to the administration of the first dose of OKT3, the second, 48 to 72 hours after administration of OKT3, and the third, approximately 2 weeks after administration of OKT3. Five of the 7 patients (71%) demonstrated a sensorineural hearing loss of 15 dB or greater at frequencies of 8 to 12 kHz. Four of the 5 patients with audiographic changes had near-complete to complete recovery of their high-frequency thresholds after discontinuation of the drug regimen. In conclusion, OKT3 can cause sensorineural hearing loss. This side effect is mainly reversible after 2 weeks following discontinuation of the drug. Patients receiving OKT3 should be forewarned of this possible side effect prior to the administration of OKT3.