Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation.

OBJECTIVE: This study aimed to investigate the prevalence of and risk factors for Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation via tracheostomy tube. METHODS: A total of 40 patients on chronic ventilation were included in a prospective cohort study. Middle-ear status was determined by tympanometry. Tympanograms were categorised as types A, B or C; types B and C were defined as middle-ear pathology. RESULTS: In all, 57 ears of 40 patients were examined. Disease was found in at least 1 ear in 26 out of 40 patients. Middle-ear pathology was found in 25 out of 34 patients who were tube fed (via nasogastric tube or percutaneous endoscopic gastrostomy) vs 1 patient out of the 6 fed orally (p = 0.014), and in 23 out of 31 with conscious or cognitive impairment vs 3 out of 9 cognitively intact patients (p = 0.044). CONCLUSION: Middle-ear pathology is common in patients on chronic mechanical ventilation via tracheostomy tube. The highest prevalence was in those with impaired consciousness or cognition, and oral feeding appeared protective.

Acquisition of early auditory milestones with a cochlear implant.

OBJECTIVE: Speech acquisition after cochlear implant is a long process. Various studies have followed the auditory milestones in the early period after implantation. The aim of the present study was to track the development of hearing skills in the early period after cochlear implantation and evaluate which factors influence the process. METHODS: 195 records of children implanted in the Hadassah Medical Center were examined retrospectively. Data on etiology, age at implantation and type of implant were collected. In addition, information on the rate of progress was measured: the first time that there was detection and identification of Ling sounds, the first time it was possible to obtain SDT (speech detection threshold), SRT (speech reception threshold) and an audiogram, and the first accurate repetition of VCV (vowel consonant vowel) sounds. RESULTS: Results show a consistent pattern of auditory milestone acquisition similar to that of normal development, from milestones that do not require decoding beginning with SDT, detection of Ling sounds followed by an audiogram which requires cooperation, to tasks that involve decoding starting with SRT and repetition of Ling sounds and finally VCV repetition. The children implanted before 24 months of age achieved the auditory milestones later than children implanted between 2 and 6 years, apparently since these tasks involve cognitive abilities which are not yet developed in the youngest children. Previous hearing experience improved the rate of acquisition of the auditory milestones and progress was faster in the second implanted ear compared to the first implanted ear. CONCLUSION: More research is needed to address the relationship between acquisition of early auditory milestones and performance with the cochlear implant later on in life.

The Hebrew and the Arabic version of the LittlEARS® auditory questionnaire for the assessment of auditory development: results in normal hearing children and children with cochlear implants.

OBJECTIVE: With more children receiving cochlear implants at an early age, there is a need for evaluation and assessment of early auditory behavior. We present the translation of the LittlEARS® Auditory Questionnaire into Hebrew and into Arabic. First the validation of the LittlEARS® Auditory Questionnaire in normal hearing children was evaluated. Second, the auditory behavior and the progress in hearing skills of a group of children with cochlear implants were assessed. METHODS: A "back-translation" method was used to translate and adapt the LittlEARS® Auditory Questionnaire into Hebrew and into Arabic. Normal hearing participants included 70 Hebrew speaking and 97 Arabic speaking parents of children from 1 to 24 months of age with normal hearing. An additional group of 42 parents of children with cochlear implants with a hearing age of up to 24 months completed the LittlEARS® Auditory Questionnaire. 27 of them completed the questionnaire more than once at intervals, so that change and development could be recorded. Scores on the LittlEARS® Auditory Questionnaire were compared to results of SIR and CAP scales and other available auditory data. RESULTS: The results of the first study show that the curves found for the Hebrew and the Arabic translations of the LittlEARS® Auditory Questionnaire are essentially similar to those previously found for other languages. These curves reflect the age dependency of auditory skills. Furthermore, in the group with cochlear implants the developmental pattern was different than that of the normal hearing group, with an initial steep increase and a later slower improvement. This trend appeared both in curves of groups and in curves of individuals (individuals whose parents completed the questionnaire at several points in time). There was a high correlation between scores on the LittlEARS® Auditory Questionnaire and results of other audiologic tests, showing validity of results with the LittlEARS® Auditory Questionnaire. CONCLUSION: Both the Hebrew and Arabic versions of the LittlEARS® Auditory Questionnaire were found to be reliable and valid tools for assessment of the development of auditory behavior in children up to the age of 24 months. Furthermore, the LittlEARS® Auditory Questionnaire in both languages is useful in monitoring the progress of children with cochlear implant.

Long-term outcomes of office-based buprenorphine/naloxone maintenance therapy.

BACKGROUND: Buprenorphine/naloxone was approved by the FDA for office-based opioid maintenance therapy (OMT), with little long-term follow-up data from actual office-based practice. 18-Month outcome data on the office-based use of buprenorphine/naloxone (bup/nx) and the impact of socioeconomic status and other patient characteristics on the duration and clinical effects of bup/nx are reported. METHODS: This retrospective chart review and cross-sectional telephone interview provide treatment retention of opioid-dependent patients receiving bup/nx-OMT in an office-based setting. 176 opioid-dependent patients from two different socioeconomic groups (high and low SES) were begun on bup/nx, started intensive outpatient treatment, and followed-up after a minimum of 18 months (18-42 months) by telephone interview to assess treatment outcome. RESULTS: 110 subjects (67%) completed the interview, 77% remained on bup/nx with no difference in retention between high and low SES groups. Those on bup/nx at follow-up were more likely to report abstinence, to be affiliated with 12-step recovery, to be employed and to have improved functional status. CONCLUSIONS: Bup/nx-OMT is a viable treatment option and when coupled with a required abstinence oriented addiction counseling program is effective in promoting abstinence, self-help group attendance, occupational stability, and improved psychosocial outcomes in both low SES and high SES patient populations over an 18-42-month period.

MRI and biologic behavior of desmoid tumors in children.

OBJECTIVE: The outcome of desmoid tumor in children cannot be reliably predicted on the basis of histologic findings. We sought to determine whether the postoperative presence of residual or recurrent tumor can be predicted on the basis of demographic variables and baseline MRI features of the tumor. We also aimed to determine how imaging features change during adjuvant treatment and how the imaging features relate to the histologic features. MATERIALS AND METHODS: Two radiologists retrospectively reviewed images from 281 MRI examinations performed at baseline and during postoperative therapy for desmoid tumor. The examinations had been performed on 17 children treated between September 1991 and March 2003. Tumor volume; distinctness of margins; involvement of bone and neurovascular bundle; and T1-weighted, T2-weighted, and STIR signal intensity and contrast enhancement pattern were recorded. Baseline imaging and demographic features were correlated with the postoperative presence of residual or recurrent tumor. Imaging changes during follow-up were compared with treatment response and outcome. The imaging features of eight tumors were compared with percentage cellularity and collagen deposition in biopsy samples obtained within 30 days of imaging. RESULTS: Baseline involvement of the neurovascular bundle approached significance as a predictor of the presence of residual or recurrent tumor (p = 0.08). Other baseline imaging and demographic features were not predictive (p > or = 0.4). Changes in imaging features were variable during follow-up. T2-weighted and STIR signal intensity may be correlated with percentage cellularity and collagen deposition. CONCLUSION: MRI has limited value in prediction of the postoperative presence of residual or recurrent desmoid tumor in children. It is useful, however, for detecting disease and monitoring postoperative adjuvant therapy.

Typhlitis in childhood cancer.

BACKGROUND: Typhlitis is increasingly recognized in children undergoing chemotherapy but is poorly characterized. The authors investigated the demographic, clinical, and imaging (ultrasonography and computed tomography [CT] scans) variables related to the diagnosis, risk, and outcome of typhlitis. METHODS: The authors reviewed the records of patients who had typhlitis (bowel wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed whether duration of typhlitis was related to bowel wall thickness, extent of colonic involvement, ascites, demographics, primary diagnosis, symptoms of typhlitis, or duration of neutropenia. To identify risk factors for typhlitis, the authors compared the demographic data and previous drug therapy of 78 patients who had typhlitis and 1231 identically treated children who did not. RESULTS: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis was associated with bowel wall thickness measured by ultrasonography (n = 68; P = 0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04). Age >16 years at cancer diagnosis was the only demographic factor associated with typhlitis (P = 0.03). Two patients died of typhlitis. CONCLUSIONS: Ultrasonography was a useful imaging modality for children with suspected typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be absent. The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.

Significance of appendiceal thickening in association with typhlitis in pediatric oncology patients.

BACKGROUND: The management of pediatric oncology patients with imaging evidence of appendiceal thickening is complex because they are generally poor surgical candidates and often have confounding clinical findings. OBJECTIVE: We sought to determine the significance of appendiceal thickening in pediatric oncology patients who also had typhlitis. Specifically, we evaluated the impact of this finding on the duration of typhlitis, its clinical management, and outcome. MATERIALS AND METHODS: From a previous review of the management of typhlitis in 90 children with cancer at our institution, we identified 4 with imaging evidence of appendiceal thickening. We compared colonic wall measurements, duration of typhlitis symptoms, management, and outcome of patients with appendiceal thickening and typhlitis to patients with typhlitis alone. RESULTS: There was no significant difference in duration of typhlitis symptoms between patients with typhlitis only (15.6+/-1.2 days) and those with typhlitis and appendiceal thickening (14.5+/-5.8 days; P=0.9). Two patients with appendiceal thickening required surgical treatment for ischemic bowel, and two were treated medically. Only one patient in the typhlitis without appendiceal thickening group required surgical intervention. There were no deaths in children with appendiceal thickening; two patients died of complications of typhlitis alone. CONCLUSION: Our findings suggest that appendiceal thickening does not predict a prolonged course of typhlitis in pediatric oncology patients, but it may indicate an increased risk of serious complications from this disease process.

Heavy chain ferritin enhances serine hydroxymethyltransferase expression and de novo thymidine biosynthesis.

We have elucidated a biochemical mechanism whereby changes in iron metabolism cause changes in folate-dependent one-carbon metabolism. Although animal and clinical studies have demonstrated that perturbations in iron status and metabolism alter folate metabolism, the biochemical mechanisms underlying these associations have yet to be identified. The effect of altered ferritin expression on folate metabolism was determined in human MCF-7 cells and SH-SY5Y neuroblastoma. Cells expressing rat heavy chain ferritin (HCF) exhibited markedly increased expression of the folate-dependent enzyme cytoplasmic serine hydroxymethyltransferase (cSHMT). These effects were not seen when rat light chain ferritin was expressed. Additionally, cSHMT expression was not altered when HCF expression was induced in MCF-7 cells cultured with supplemental ferric citrate. This indicates that cSHMT expression is increased by elevated HCF concentrations, independent of increased iron availability, suggesting that cSHMT expression may respond to HCF-induced chelation of the regulatory iron pool. Increased HCF expression did not alter cSHMT mRNA levels, but did increase translation rates of cSHMT mRNA. The increase in translation was mediated, at least in part, through the cSHMT 5'-untranslated region of the transcript. MCF-7 cells with increased expression of cSHMT displayed increased efficiency of de novo thymidylate biosynthesis, indicating that thymidylate synthesis is normally limited by cSHMT activity in MCF-7 cells. Our data suggest that the iron regulatory pool may play an important role in regulating folate metabolism and thereby thymidine biosynthesis.

Bone conduction experiments in humans - a fluid pathway from bone to ear.

Animal experiments in this laboratory have led to the suggestion that a major pathway in bone conduction stimulation to the inner ear is via the skull contents (brain and CSF). This hypothesis was now tested in humans. Auditory nerve brainstem evoked responses could be recorded in neonates to bone conduction stimulation over the fontanelle and audiometric responses were obtained in neurosurgical patients with the bone vibrator on the skin over a craniotomy. There were no differences in threshold between these responses and those obtained to bone conduction stimulation over skull bone in the same subjects. Audiometric thresholds in response to bone vibrator stimulation of the eye (a 'natural craniotomy') were no different from those to bone stimulation delivered to several sites on the head. Thus there is no need to vibrate bone in order to obtain 'bone conduction' responses. Bone vibrator thresholds to stimulation at the head region with thinnest bone (temporal) were better than those to stimulation at the forehead region which has much thicker bone, implying that the vibrations penetrate the skull at the site of the vibrator. In addition, the magnitude of vibration (acceleration) measured at various sites around the head in response to bone vibrator stimulation at a fixed point on the forehead generally decreased with distance from the point of vibration. Therefore it seems that the vibrations produced by a bone vibrator at a point on the head are also able to penetrate the skull, setting up audio-frequency pressures in the CSF which spread by fluid communications to the inner ear fluids, exciting the ear.

Transient evoked otoacoustic emissions in newborns in the first 48 hours after birth.

Newborns are often discharged from hospital at the age of about 48 hours. At this age, transient evoked otoacoustic emissions (TEOAEs) are not necessarily recordable in all healthy newborns. In order to determine the factors which would enable the successful recording of TEOAEs before discharge to facilitate screening for hearing, 65 fullterm newborns under 48 hours of age were tested, the youngest being 10 hours old. The ears of those neonates in whom TEOAEs could not be obtained (N = 7 neonates bilaterally, 6 unilaterally) were examined otoscopically, cleaned of vernix and retested for TEOAEs. We were thus able to record in at least one ear in all neonates tested, if the ears were clean, if they were asleep and if the testing room was quiet.

Audiovestibular findings in patients with deafness caused by a mitochondrial susceptibility mutation and precipitated by an inherited nuclear mutation or aminoglycosides.

OBJECTIVE: To characterize the audiological and vestibular changes associated with a mitochondrial DNA mutation in an Arab-Israeli family and in other families with mitochondrial predisposition to aminoglycoside-induced hearing loss. DESIGN: Evaluation of audiological (pure tone thresholds, speech reception thresholds, speech discrimination, tympanometry, acoustic reflex thresholds, tone decay, and auditory brain-stem evoked response recording) and vestibular (complete history, physical examination, and 2-channel electronystagmography) systems. In 5 patients, structural evaluation of the inner ear was done by magnetic resonance imaging. PATIENTS: Fifteen members of an Arab-Israeli family, and 1 Chinese woman with the same mitochondrial DNA mutation who experienced hearing loss after short-term exposure to streptomycin. RESULTS: Most of the patients had a profound hearing loss due to cochlear involvement. The hearing loss usually was not accompanied by notable peripheral vestibular dysfunction. In the patient with severe hearing loss after exposure to aminoglycoside, the vestibular function was completely normal. CONCLUSIONS: In most of the Arab-Israeli patients with congenital deafness, the vestibular system function was normal, in contrast to the frequency of vestibular abnormality among deaf children, which was described in the literature. This may be related to genetic predisposition to aminoglycoside-induced deafness.

Mandatory toxicology testing and chemical dependence consultation follow-up in a level-one trauma center.

OBJECTIVE: There is a growing body of evidence indicating an association between intoxication and major trauma. This study assessed the prevalence of alcohol or drug intoxication in major trauma admissions to an urban trauma center. DESIGN: Sequential case series. METHODS: Toxicology testing and structural clinical interview assessment. MAIN RESULTS: Seventy-eight percent of patients tested had positive toxicology results. Chemical dependence assessments performed on patients who tested positive revealed that 94% met the criteria for a substance dependence or abuse disorder. CONCLUSIONS: The implications of this data for admission toxicology testing policies and chemical dependence consultation support services to trauma units are discussed.

Neonatal auditory brain-stem response threshold and latency: 1 hour to 5 months.

Auditory brain-stem evoked responses were recorded in normal neonates and infants ranging in age from less than 1 h to 5.5 months. The average threshold in neonates 0-5 h old was 29 dB greater than that in adults, reaching the adult threshold range within 2 weeks. The latency of wave I in 0-5 h neonates was 1.81 msec and reached the adult range within 2 weeks. The V-I interpeak latency in 0-5 h neonates was 5.3 msec and did not reach adult values within the period of this study.

Auditory nerve and brain stem evoked response thresholds in infants treated with gentamicin as neonates.

Thirty-two infants (18 full-term and 14 premature) who had been treated with gentamicin as neonates were examined to ascertain whether this drug induced hearing loss, even of low severity. Objective thresholds to clicks were obtained using auditory nerve and brain stem evoked responses. In addition, behavioral audiometry was performed. Serum concentrations before and after gentamicin treatment were at therapeutic levels. All infants were examined at least 1 1/4 months after cessation of therapy. Normal thresholds were obtained in all ears, with the exception of two with demonstrable middle ear effusion. It appears that gentamicin in therapeutic doses and serum concentrations, in the absence of renal insufficiency, does not cause hearing loss in neonates.