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Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group.

BACKGROUND: Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma. OBJECTIVE: We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray. METHODS: A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements. RESULTS: Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed. CONCLUSION: Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.

Adolescent↗

Clinical presentation as a guide to the identification of GERD in children.

OBJECTIVE: to determine if there is a correlation between common otolaryngologic symptoms and presence of gastroesophageal reflux disease (GERD) in children. METHODS: charts of 295 children presenting with suspicion of GERD were reviewed for presenting symptoms including: (1) airway symptoms: stertor, stridor, frequent cough, recurrent croup, wheezing, nasal congestion, obstructive apnea, blue spells, hoarseness, throat clearing; (2) feeding symptoms: wet burps, globus sensation, frequent emesis, dysphagia, choking/gagging, sore throat, halitosis, food refusal, stomach aches, arching, drooling, chest pain, irritability, and failure to thrive. At least one positive test of barium esophagram, gastric scintiscan, pH probe or esophageal biopsy resulted in inclusion in the GERD positive group. RESULTS: 214 children had GERD diagnosed while 81 had no positive tests for GERD. Between the GERD positive and GERD negative groups, the significantly different symptoms were stertor (P=0.040), cyanotic spells (P=0.043), frequent emesis (P=0.007), failure to thrive (P=0.006), and choking/gagging (P=0.044). Three pooled variables were created: airway flow (stertor, stridor, cyanotic spells), airway irritation (frequent cough, recurrent croup, throat clearing), and feeding (dysphagia, failure to thrive, frequent emesis). GERD patients who were 2 years or less were compared to those older than 2 years and all three of these pooled variables were significantly different between these groups (P<0. 001). CONCLUSION: children who present with a certain constellation of airway or feeding symptoms are more likely to have a positive GERD test. Children 2 years old or less are more likely to present with airway symptoms or feeding difficulties while children older than 2 years are more likely to present with airway irritation.

Airway Obstruction↗

Clear cell carcinoma of the larynx--a case report.

Clear cell carcinoma (CCC) of the larynx is extremely rare and to the best of our knowledge no such case has been reported in the paediatric age group. These tumours resemble the clear cell carcinoma of the major and minor salivary glands. We report such a lesion in a 15 years old boy presenting with hoarseness and an exophytic growth in the glottis. A frontolateral conservation laryngectomy with laryngoplasty was done and over 2 years follow-up has shown no evidence of loco-regional recurrence and he enjoys an acceptable voice.

Adenocarcinoma, Clear Cell↗

Otorhinolaringologic manifestation of Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation (MCA/MR) syndrome link to a contiguous-gene deletion syndrome, involving chromosome 1 7p 11.2,whose incidence is estimated to be 1:25,000 livebirth. SMS is characterised by a specific physical, behavioural and developmental pattern. The main clinical features consist of a broad flat midface with brachycefaly, broad nasal bridge, brachydactily, speech delay, hoarse deep voice and peripheral neuropathy. Behavioural abnormalities include hypermotility, self-mutilation and sleep disturbance. This report defines the otorhinolaryngological aspects of a new case of SMS, confirmed by cytogenetic-molecular analysis, in a 9 year old girl affected by chronic otitis media, deafness and sinusitis, who presented with typical clinical signs and symptoms.

Abnormalities, Multiple↗

Upper airway obstruction in Hunter syndrome.

Patients with Hunter syndrome may have symptoms of hoarseness, stridor and breathing difficulties as a result of laryngeal and tracheal involvement. In planning their evaluation, we must prefer non-invasive methods as X-ray or CT scan, and avoid doing endotracheal intubation or bronchoscopies. Review of adult cases in the literature and description of the only case of a child with Hunter syndrome having life-threatening complications of his upper airways is discussed in this report. In this case and in the literature we cannot exclude intubation or bronchoscopy as a serious aggravating factor, causing further narrowing of the larynx.

Bronchoscopy↗

Longitudinal survey of voice quality after pediatric laryngotracheoplasty.

This study assesses the effect of pediatric laryngotracheoplasty on voice quality. A group of ten children who underwent laryngotracheoplasty with thyrotomy and anterior cartilage graft were examined two or more times after decannulation and their voices were compared to those of sex- and age-matched controls. Each examination included a laryngoscopy, evaluation by a speech/language pathologist and measurement of maximum phonation times and fundamental frequencies using the Signalyse program. The strength of the voices and the maximum phonation times gradually improved. The fundamental frequency became lower with age, as in the controls. The data suggest that laryngotracheoplasty does not hamper the development of voice with age in children and that the voice improves without any further surgery, although hoarseness remains.

Adolescent↗

Dysphonia in infants.

The definition of infant dysphonia is difficult because the physiological phonation itself may be extremely variable in newborns. In a wider sense, all voice utterings can be interpreted as dysphonia which deviate continuously in any of the parameters (timbre, pitch, intensity, or noise) from the normal. We differentiated 20 types of such pathological phonation. The most characteristic are: the hoarse (caused by inflammation or tumor of the vocal cords); the hollow (indicative of tracheal stenosis); the shrill (suggesting a CNS damage); the bleating (pathognostic of Down syndrome); the faint (a result of myogenic diseases); and the mewing cry (etiology: cri-du-chat syndrome). In a narrower sense dysphonia in infants is a kind of pathological phonation without evidence of neurological alteration or chromosomal aberration and without a verified laryngeal lesion. These infants utter pressed, harsh, or very high voice (hyperfunctional form) or a weak, inert cry (hypofunctional form). The dysphonic voice may be characterized also by sudden change in melody or in pitch (glide, shift, break, bitonality) and by turbulent noises. This type of newborn dysphonia is a result of the immature innervation of the larynx, it gradually improves and lateron spontaneously disappears. Perceptual evaluation, endoscopy, and acoustic analysis yield useful diagnostic information.

Crying↗

Voice problems in children: pathogenesis and diagnosis.

Voice problems seem to concern more than one child out of twenty, and may concern quality (hoarseness), resonance (nasality), pitch (mutation) and loudness. The main etiological categories are defined as organic (congenital/acquired), functional/habitual (especially due to voice abuse and misuse), and psychogenic (especially mutation disorders). Flexible transnasal endoscopes of small diameter (2.3 mm) are optimally suited for accurate endoscopic diagnosis, especially if combined with video-recording and stroboscopy.

Child↗

Juvenile onset recurrent respiratory papillomatosis: possibilities for successful antiviral therapy.

Recurrent respiratory papillomatosis (RRP) is a potentially devastating disease that can have significant morbidity, and can even result in mortality due to airway compromise or, less commonly, malignant transformation. Two distinct types of RRP exist: adult-onset RRP (AO-RRP) and juvenile-onset RRP (JO-RRP). Acquisition of human papillomavirus (HPV), the causative agent of RRP, is believed to occur in the peripartum period in the case of JO-RRP, with disease symptoms (primarily hoarseness) becoming apparent during the first several years of life. Treatment currently consists of surgical debulking of the papillomas to relieve airway obstruction. However, numerous antiviral therapies have also been evaluated, albeit primarily under uncontrolled settings. This article will review the biology, natural history and management of HPV infection, with particular emphasis on JO-RRP.

Adolescent↗

Neck dissection following radiochemotherapy of advanced head and neck cancer--for selected cases only?

PURPOSE: To address the value of neck dissection (ND) in patients with advanced head and neck cancer following primary radiochemotherapy and to specifically analyse its impact on locoregional tumour control, survival and toxicity. PATIENTS AND METHODS: Between 1987 and 1997 (9,335), a total of 142 patients (pts) were treated by primary radiochemotherapy (RCT) according to prospective protocols. There were 64 pts with involvement of the hypopharynx, 57 pts with oropharyngeal and 21 with oral cavity carcinoma. UICC (1997) stages included: 16 pts in stage III, 113 pts in stage IV A, 13 pts in stage IV B. All pts received platin-based RCT up to a median total dose of 70 Gy (range, 60-72 Gy). Six weeks after RCT, pts with complete response of the primary tumour (N=97) were offered a uni- or bilateral ND depending on the initially diagnosed nodal disease as part of a strict institutional policy. Fifty-six pts consented to ND and 41 refused. These two groups were analysed in terms of characteristics, local and regional tumour control, survival and long-term side effects. Median follow-up was 37 months (range, 22-124 months). RESULTS: Among the 56 pts receiving ND, a total of 13 (23%) was found to have residual tumour in the neck specimen. The rates of positive histology according to clinical N category after RCT were: yN0 (2/22[9%]), yN1 (2/10[20%]), yN2a-b (2/10[20%), yN2c-3 (7/14[54%]). Five-year overall survival and disease-specific survival rates for pts with ND were 44 and 55%, for pts without ND 42 and 47%, respectively (P=0.9). No difference was seen for long-term local and regional control between the two patient groups. Comparing the group of patients with and without ND, a trend towards higher subjective morbidity of grade 3 and 4 (LENT-SOMA), i.e. pain recording (24% vs. 17%), dysphagia (48% vs. 35%) and hoarseness (20% vs. 9%) was evident in patients with ND. CONCLUSION: No clear evidence for routine clinical use of ND after RCT in advanced head and neck tumours can be derived from these data. ND may be contemplated in selected cases with multiple residual nodes only.

Adult↗

Predictive role of HER-2/neu overexpression and clinical features at initial presentation in patients with extensive stage small cell lung carcinoma.

Although recent advances in therapy have improved the quality of life in patients with extensive stage small cell lung cancer (ESSCLC), prolonged survival is still uncommon. To determine the role of HER-2/neu overexpression and other clinical predictors (symptoms at presentation) of adverse outcome in ESSCLC, we performed a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or = 2+ was considered positive for overexpression. Between 1991 and 2000, 223 patients with ESSCLC were identified, of whom 193 patients (84 females, 109 males) with a mean age of 68.5 years (range: 42-90 years) had adequate tissue specimens for HER-2/neu testing. The symptoms at initial presentation and proportionate number of patients were: weight loss 61 (31.6%), cough 53 (27.5%), dyspnea 33 (17.1%), mass on chest radiograph 18 (9.3%), chest pain 15 (7.7%), asymptomatic 14 (7.2%) and others (weakness, lymphadenopathy, hoarseness and paraneoplastic syndromes) 29 (15.0%). Of the 193 specimens, 57 (29.5%) revealed HER-2/neu overexpression. The median survival for patients with ESSCLC who were HER-2/neu positive was 8 months (range: 1-25.5 months) while that in the HER-2/neu negative group was 16 months (range: 2-34 months). Interestingly, after adjusting for age, performance status and type of therapy, subset analysis revealed that the survival was significantly lower in HER-2/neu positive individuals (P<0.001; Mann-Whitney U-test). In our study, weight loss and cough were the two most common (59%) presenting complaints in patients with ESSCLC. Also, since HER-2/neu positivity was a marker for poor prognosis in ESSCLC, testing for overexpression may play a role in identifying patients at risk for shortened survival. Further studies would delineate whether HER-2/neu overexpression renders SCLC chemoresistant and thus, adversely affects outcome. There exists a need for randomized controlled trials to assess the role of Herceptin (alone or in combination with standard chemotherapy) in patients with ESSCLC.

Adult↗

The role of topotecan in treating small cell lung cancer: second-line treatment.

Small-cell lung cancer (SCLC) is highly chemosensitive but up to 70% of patients with limited disease and more than 90% of patients with extensive disease will relapse after first-line treatment. There are several standard chemotherapy regimens used for second-line treatment yet the prognosis for patients requiring this treatment remains poor. The topoisomerase-I inhibitor, topotecan, has achieved response rates of up to 22% in previously treated patients with SCLC and survival almost double that achieved with other single agents. Compared with cyclophosphamide/doxorubicin/vincristine (CAV), single-agent topotecan achieved a higher response rate, longer survival and statistically significant improvements in dyspnea, hoarseness, fatigue, anorexia and interference with daily activities. Brain metastases are common in SCLC. Topotecan crosses the blood-brain barrier and shows promise for the management of brain metastases.

Administration, Oral↗

Malignant melanoma and dermatofibrosarcoma in a 60-year-old patient with lifelong acrodermatitis enteropathica.

The life course of acrodermatitis enteropathica is recorded in a 62-year-old white man. Initially saved in infancy by breast-feeding and good medical care, later in his twenties he responded well to diiodohydroxyquinoline (Diodoquin) therapy, his only residua being dermatitis, hoarseness, and short stature. Subsequently untreated, this patient years later developed not only a dermatofibrosarcoma but also a large amelanotic malignant melanoma. Both were successfully excised. Subsequently, oral zinc therapy initiated for the first time cleared his acrodermatitis, which had been present for 60 years. It is suggested that this patient's malignancies developed as a result of an immune deficiency state typically found in acrodermatitis enteropathica. On this basis, acrodermatitis enteropathica may be viewed as having a malignant potential over the long term. The zinc-dependent nature of the immune deficit, however, suggests that lifelong daily zinc supplementation is an appropriate prophylactic measure.

Acrodermatitis↗

Pachyonychia congenita.

Pachyonychia congenita is a rare hereditary disorder characterized mainly by nail hypertrophy and dyskeratoses of skin and mucous membranes. A thorough literature survey since its first description in 1904 up to 1985 revealed 168 cases of pachyonychia congenita. There were no indications of any sex or ethnic group predilection. Based on this survey the following classification is suggested: type I (56.2% of cases), hyperkeratosis of nails, palmoplantar keratosis, follicular keratosis, and oral leukokeratosis; type II (24.9% of cases), clinical findings of type I plus bullae of palms and soles, palmar and plantar hyperhidrosis, natal or neonatal teeth, and steatocystoma multiplex; type III (11.7% of cases), clinical findings of types I and II plus angular cheilosis, corneal dyskeratosis, and cataracts; and type IV (7.2% of cases), clinical findings of types I, II, and III plus laryngeal lesions, hoarseness, mental retardation, hair anomalies, and alopecia.

Humans↗

Unilateral true vocal fold paralysis: cause of right-sided lesions.

At the Georgetown University Center for the Voice, 778 patients were referred for evaluation between July 1, 1990, and June 30, 1995. During this 5-year period, right true vocal fold paralysis or paresis was diagnosed in 24 of these patients (3%). Videostroboscopy, voice analysis, and patient records were reviewed. Ages ranged from 23 to 80 years, and sex distribution approximated a 1:1 ratio. The patients presenting symptoms included hoarseness, dysphagia, choking, voice pitch change, voice weakness, fatigability, and breathiness. Sources of the vocal fold dysfunction included iatrogenic, traumatic, central, and infectious causes.

Adult↗

Gastroesophageal reflux disease: symptoms versus pH monitoring results.

OBJECTIVES: The reason why some patients with gastroesophageal reflux disease (GERD) have symptoms of upper aerodigestive system irritation, while others mainly have gastroenterologic symptoms, is not well established. This retrospective case series study was designed to examine the existence of a correlation between symptoms and reflux characteristics, based on data obtained from esophageal pH monitoring. METHODS: The study population consisted of 139 patients; 97 patients presented with laryngopharyngeal symptoms of GERD, including unexplained hoarseness, throat clearing, chronic cough, laryngospasm, globus, throat pain, and 42 patients presented with gastroenterologic symptoms, including heartburn and regurgitation. The results of 24-hour, double-channel ambulatory esophageal pH monitoring were analyzed comparing 2 symptom groups. The incidence of abnormal acid reflux at the upper and lower esophageal segments and the effects of upright and supine positions on reflux parameters were evaluated. RESULTS: The incidence of laryngopharyngeal reflux was significantly higher in the laryngopharyngeal symptom group than in the other (52% versus 38%). The patients with laryngopharyngeal reflux from both groups showed no significant differences in terms of number of acid reflux episodes, percentage of times pH was 4, and esophageal acid clearance. Upright and supine parameters did not show significant differences between the patient groups. Upright acid reflux episodes were, however, common in both groups at the lower esophageal and laryngopharyngeal segments. CONCLUSION: Recent studies suggesting that otolaryngologic patients commonly show upright, daytime reflux with normal esophageal clearance and that typical GERD patients commonly have supine, nocturnal reflux with prolonged esophageal clearance are not supported by this study. This study indicates that acid reflux parameters and positional changes are not sufficient to explain why patients with GERD experience different symptoms. The regional symptoms of GERD may be attributed to the impairment of epithelial resistance, motor activity, and buffering systems for the esophageal antireflux barrier.

Adult↗

Prospective, longitudinal quality-of-life study of patients with head and neck cancer: a feasibility study including the EORTC QLQ-C30.

Despite modern advances in the treatment of head and neck cancer, the survival rate fails to improve. Considering the different treatment modalities involved, quality of life has been thought of as an additional end point criterion for use in clinical trials. A Nordic protocol to measure the quality of life of head and neck cancer patients before, during, and after treatment was established. Before the study, a pilot study was done with this protocol. The main purpose of this pilot study was to find out whether this cancer population would answer quality-of-life questionnaires repeatedly (six times) over a 1-year period and whether the chosen questionnaires-a core questionnaire (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)), a tumor-specific questionnaire, and a psychological distress measure (Hospital Anxiety and Depression scale (HAD))-were sensitive for changes to functions and symptoms during the study year. The results presented in this article all refer to the pilot study. Forty-eight consecutive patients agreed to participate in the study. The most common tumor locations were the oral cavity (17) and the larynx (12). Almost all patients received combined treatment: 45 of 48 radiation therapy, 18 of 48 chemotherapy, and 17 of 48 surgery. After the primary treatment, 40 patients had complete tumor remission. Four of the 48 patients did not answer any questionnaires and were therefore excluded from the study. Of the remaining 44 patients, 3 died during the study year, and another 6 withdrew for various reasons. Thirty-five (85%) of the 41 patients alive at the 1-year follow-up answered all six questionnaires and thus completed the study. Mailed questionnaires were used throughout the study. All questionnaires were well accepted and found to be sensitive to changes during the study year. The greatest variability was found for symptoms and functions related specifically to head and neck cancer. The symptoms were swallowing difficulties, hoarse voice, sore mouth, dry mouth, and problems with taste. They all showed the same pattern, with an increase of symptoms during and just after finishing the treatment. The HAD scale revealed a high level of psychological distress, with 21% probable cases of psychiatric morbidity at diagnosis. In conclusion, it was shown that the study design and questionnaires were feasible for the forthcoming prospective quality-of-life assessment of Swedish and Norwegian head and neck cancer patients.

Adult↗

Stretch-induced nerve injury as a cause of paralysis secondary to the anterior cervical approach.

The anterior approach to the cervical spine, first described 40 years ago, has become a popular and widely used procedure by spine surgeons to expose the anterior vertebral bodies from C3 to T1. A significant complication of this procedure is transient or permanent ipsilateral recurrent laryngeal nerve paralysis. In a previous review at our institution of patients with hoarseness after an anterior cervical approach, 15 of 16 patients demonstrated right-sided paralysis. The asymmetry in the anatomic courses and lengths of the recurrent laryngeal nerves are proposed to place the right recurrent laryngeal nerve at an increased risk of stretch-related injury during this surgical procedure. We developed a cadaver model to evaluate the in-line stretch on the recurrent laryngeal nerve during the right- and left-sided approaches to the C4 and C7 vertebral bodies. To assess the difference in risk of injury to the two recurrent laryngeal nerves, we performed the anterior approach to the cervical spine in four anatomic positions: the left neck and right neck at the levels of C4 and C7 on 10 fresh human cadavers during the immediate postmortem period. The blades of a Cloward retractor were progressively spread to 2, 3, and 4 cm in the four anatomic positions while the corresponding degrees of ipsilateral recurrent laryngeal nerve stretch resulting from retraction were simultaneously measured. The left recurrent laryngeal nerve had sufficient redundancy in its course within the tracheoesophageal groove in 10 of 10 cadavers such that it exhibited no in situ stretch during the left-sided approach to either the C4 or C7 vertebrae. In contrast, the right recurrent laryngeal nerve has little redundancy in its course and is not protected within the tracheoesophageal groove. The right-sided approach to C7 resulted in an average in situ stretch on the ipsilateral recurrent laryngeal nerve of 12% and 24%, with 3 cm and 4 cm of Cloward retraction, respectively. The right-sided approach to C4 resulted in significant levels of stretch in 3 (30%) of 10 cadavers and no stretch in 7 (70%) of 10 cadavers. The relevance of these data is demonstrated by the review of numerous studies demonstrating the potential for significant neural damage with nerve stretch greater than 12%.

Aged↗