Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr virus.

Kinetics of cell growth of human B-lymphocyte lines derived from Burkitt's lymphomas and lines derived from the Epstein-Barr virus transformation of normal adult lymphocytes were studied. Cells seeded at high densities (5 X 10(4)/ml) grew in an exponential manner; those seeded at low densities (5 X 10(3) to 1 X 10(4) began to grow exponentially only after a lag period of 3 to 4 days. Transfer of stationary low-density cell populations into filtered media from growing high-density cultures (conditioned media) stimulated cell growth, as determined both by increased cell numbers and [3H]thymidine incorporation. Enhanced cell growth occurred in conditioned media at all cell seeding concentrations that grew in normal media. Furthermore, cultures seeded at very low cell concentrations that do not grow in normal media proliferated in conditioned media. Media from a series of B-cell lines tested with one exception were autostimulatory. Reciprocal cell transfer experiments showed that media from B-cell lines cross-stimulated cells in other B-cell lines. Media from the non-B-cell lines tested were not autostimulatory and did not stimulate growth of the B-cell lines, and conversely these non-B-cell lines were not growth enhanced by the conditioned media. Absorption of growth-enhancing media with preincubated cell lines seeded at low density removed the enhancing capacity. These results demonstrate that B-cell lines from Burkitt's lymphomas and B-cells transformed in vitro by Epstein-Barr virus produce absorbable growth-enhancing factor(s) that may be essential to the development of perpetual growth in culture.

An animal model for the assessment of microvascular patency.

A tubed superficial epigastric flap (TSEF), based on a single vascular pedicle, was designed in a rat. Forty TSEFs were created in three control groups: in 20 TSEFs both the femoral artery and vein were ligated proximal to the take-off of the superficial epigastric vessels, in 10 TSEFs the femoral artery and in the other 10 the femoral vein were ligated and transected at the same location. All TSEFs in the control groups sloughed, reflecting the dependence on the axial vasculature. A further 232 TSEFs were made with a survival rate of 84.5% (196/232). Delayed arterial or venous ligation was then performed up to 42 days after the initial surgery. The patency of the axial vein was crucial for survival for only the first postoperative week. The axial arterial patency was needed for survival of the TSEF for 6 weeks. The creation of this TSEF fulfills the need for a simple model that is as readily constructed as other models, is reproducible, has a high success rate and most importantly, reflects the patency of its nutrient vessels for a prolonged period of time.

The importance of the pedicle for the survival of a vascularized free flap: an experimental study on rats.

It has been assumed, but never shown experimentally, that the survival of a free vascularized full-thickness island flap is based on the vascular pedicle. A study using the rat was designed to assess the three parameters of flap survival: the vascular pedicle, the recipient bed, and the perimeter of the recipient area. Isolation of the pedicle by ligation caused flap necrosis in 18 out of the 20 groin flaps. An intact pedicle, with the other two parameters excluded, led to flap survival in 75% (9 of 12 flaps). Our results indicate that the critical factor to island flap survival in the immediate postoperative period is the vasculature supplying the pedicle. The two other factors are of limited importance.

Snoring, obstructive sleep apnea, and surgery.

Snoring and OSA syndrome are prevalent and important causes of sleep disturbance. Snoring, historically considered to be only a habitual annoyance, has significant physical and social consequences. OSA is now considered to be a major public health concern with significant morbidity and mortality. CPAP is considered the treatment of choice for OSA syndrome, but poor patient acceptance and compliance remain problematic. Surgical procedures have been developed to alter the offending anatomic abnormalities responsible for OSA. Identification of the offending anatomic site with application of the most appropriate surgical procedure is essential for effective surgical treatment of OSA. When the region of the retropalate is correctly identified as the site of obstruction, UPPP can effectively treat OSA in a majority of patients. Surgical correction of nasal obstruction is advocated in conjunction with sleep apnea surgery when nasal obstruction exists. In OSA patients with retrolingual airway obstruction, a number of surgical procedures have been performed, with or without UPPP, with some improvement over UPPP alone. MMO has been effective in the treatment of OSA in patients with significant retrolingual airway obstruction with contributing skeletal abnormalities and in patients who have failed multiple other surgical procedures. MMO, however, is a procedure of considerable magnitude, requiring extensive oromaxillofacial surgical expertise. MMO is likely appropriate only in a limited number of patients. Tracheostomy is completely effective in the treatment of OSA syndrome but is undesirable to patients and is associated with significant physical and emotional morbidity. Nonetheless, tracheostomy can be lifesaving and remains an option for patients with severe OSA with serious associated cardiovascular complications, who cannot tolerate CPAP, and for whom other interventions are ineffective or unacceptable. Effective surgical treatment of snoring has been accomplished with UPPP and LAUP. LAUP is less invasive, less morbid, more cost-effective, and better tolerated and is likely the most appropriate procedure for debilitating symptomatic snoring. Currently, LAUP is not recommended for the treatment of OSA, despite some efficacy in patients with mild OSA. Exclusion of OSA in patients undergoing LAUP for snoring is important.

Obstructive sleep apnea in Down syndrome children: a surgical approach.

Obstructive sleep apnea is considered in five Down syndrome children. All had altered anatomy consistent with this syndrome involving the oropharynx, cranium, and midface. Based on earlier work, it was established that, except for specific isolated instances, routine tonsillectomy and adenoidectomy would not reverse obstructive respiratory patterns in this patient population. A modified pharyngopalatal surgical approach has been successful in alleviating upper airway sleep obstruction in Down syndrome.

Thymic cysts in the neck.

The etiologic considerations in head and neck lesions rarely include the diagnosis of thymic cysts. A correlative summary of three new cases was analyzed with respect to the already existing body of data. A classification of thymic cysts, their embryogenesis, clinical signs, and appropriate pre-operative studies were stressed. The gross and microscopic histopathology was reviewed with the conclusion that in many instances normal thymus was included in the surgical specimen. Given our increasing knowledge regarding thymic function, it was stressed that heightened awareness of this clinical entity should enable preservation of the normal thymus gland.

Pseudomonas rhinosinusitis.

Although rare in the otherwise healthy patient, pseudomonas rhinosinusitis is encountered most frequently in the immunocompromised host or severely traumatized patient. Intravenous antibiotic therapy in conjunction with aggressive surgical drainage is required. Two cases are documented that are typical of this philosophy. A third patient with isolated nasal involvement, because of multiple medical disabilities, was treated with local debridement and topical therapy alone and responded.

Hyperlipidemia in association with childhood sensorineural hearing loss.

In adults there has been an association noted between hyperlipidemia and sensorineural hearing loss. Etiologic considerations include hyperviscosity of the serum, vascular occlusion and an increased susceptibility to noise. Until now this correlation, to our knowledge, has not been made in the pediatric population. Several children with bilateral fluctuating sensorineural hearing losses have been identified with hyperlipidemia. The fluctuations in hearing varied with lipid levels. With dietary controls, the cholesterol levels returned to what would be near the norm for the pediatric population and hearing returned to near baseline. Unexplained fluctuating sensorineural hearing losses in children warrant the consideration of hyperlipidemia. Discovering a potentially reversible etiology for hearing loss is significant but more importantly, may lead to the early detection of hyperlipidemia in the young patient.

A comparison of preservation techniques in a vascularized rat laryngeal transplant model.

In earlier laryngeal transplantation studies by Takenouchi, et al., the longest ischemic interval tolerated was 45 minutes. A new animal model and enhanced preservative solutions made reassessment timely. This study evaluated two determinants of graft viability: 1. the duration of ischemia and 2. the composition of the preservative media. Three groups of viable transplants were assessed. Groups I and II were preserved with iced heparinized saline with respective ischemic intervals of 3 and 6 hours. Group III was preserved with the Wisconsin solution during a 20-hour ischemic interval. All animals were sacrificed at 24 hours. Representative sections of group I confirmed viability whereas group II exhibited both clinical and histologic evidence of irreversible vascular change. In contrast, most representative sections in group III had little demonstrable change. These data suggest that laryngeal allografts can endure prolonged ischemic intervals if properly maintained.

Vagaries of thyroglossal duct cysts.

The thyroglossal duct cyst is the most common congenital cyst found in the neck, classically presenting as a paramidline mass in a healthy young adult. Fifty-three cases managed at the Brigham and Women's Hospital and Boston's Beth Israel Hospital over the past 10 years were reviewed. The unique presentation of papillary adenocarcinoma in TGDCs and findings in the elderly population are discussed. These cases represent both diagnostic and therapeutic challenges. The existing literature is correlated with our data, providing a treatise on management.

Dysphagia in patients with inclusion body myositis.

OBJECTIVES: Inclusion body myositis (IBM) is an inflammatory myopathy with a 40% reported incidence of dysphagia. A protracted course, refractory to medical therapy, frequently leads to consultation with an otolaryngologist for dysphagia management. We studied the incidence, symptoms, and mechanisms of dysphagia in patients with IBM. STUDY DESIGN: Retrospective study of medical records and self-reported follow-up survey; dysphagia is defined as difficulty in swallowing. MATERIALS: Twenty-two patients with biopsy-proven IBM. RESULTS: The rate of dysphagia was more than 80% (16 of 19), twice as high as previously reported. Progressive dysphagia was associated with a significantly worse functional class. Relevant management guidelines are established, including the timing for appropriate surgical intervention. CONCLUSION: Progressive dysphagia may signify more aggressive IBM or an episodic worsening in status. Recognition of the disease manifestations will afford proper patient management. Informed otolaryngologists can have a favorable impact on the dysphagia associated with IBM.

Ludwig's angina: an update.

Despite a reduction in preantibiotic mortality rates that exceeded 50%, Ludwig's angina remains a potentially lethal entity primarily because of rapidly progressive airway obstruction. Since the reports of several large series in the 1940's, there have been put sporadic case reports because of widespread use of antibiotics in orodental infection, improved dental care, as well as adherence to strict diagnostic criteria. Since this entity is now uncommon, unnecessary delay in diagnosis and management may occur and may result in serious complications. This presentation will consist of an historical review, discussion of pathogenesis followed by clinical presentation, bacteriology and treatment, as well as a detailed analysis of our most recent 20 cases. There were no complications and no deaths. The infection resolved with medical therapy in 11 patients, while 9 patients required surgical procedures. Penicillin, clindamycin or chloramphenicol were started initially in all cases. Four of these 9 patients developed a localized abscess, while on antibiotics, which required drainage. Tracheotomy or intubation was necessary in 7 patients. Early and aggressive use of appropriate antibiotics and protection of the airway are the mainstays of a successful treatment regimen. Judicious surgical intervention is indicated in those patients who develop localized abscesses while on antibiotics or are unresponsive to medical management.

Bilateral congenital middle ear cholesteatomas.

Congenital middle ear cholesteatomas remain of interest because of their relative rarity and unknown origin. A 4-month-old child presenting with bilateral congenital middle ear cholesteatomas forms the basis for this report. The nature of the epithelial debris found suggests an external origin. An extended transcanal tympanotomy approach for removal, based upon an operative experience of 11 similar ears, will be discussed.

Effect of mechanical reinforcement on stability of the rotary door flap laryngotracheal reconstruction: a canine study.

OBJECTIVE/HYPOTHESIS: The rotary door flap (RDF) laryngotracheal reconstructive procedure uses a 180 degrees rotation of the sternohyoid muscle into a laryngofissure. Despite excellent clinical results, there are concerns of flap inspiratory prolapse. This study examined RDF stability and the efficacy of ancillary materials in providing additional support. METHODS: Seventeen dogs underwent endoscopic induction of subglottic stenosis and delayed RDF reconstruction. Animals received 1) traditional RDF (control), 2) RDF with titanium screen implant, 3) RDF with porous polyethylene implant, or 4) RDF with hydroxyapatite cement (HAC) injection. Four weeks postoperatively the flaps were tested for stability. On qualitative assessment, endoscopic visualization was completed with quiet respiration and then following endotracheal tube occlusion. On quantitative assessment, after animals were killed, the RDF segment was isolated and subjected to negative pressure (maximum pressure, -50 mm Hg). The pressure-causing collapse was measured. RESULTS: In the traditional RDF animals (control), five of six flaps were stable in vivo and with negative pressures. In the titanium screen, porous polyethylene group, and HAC groups, respectively, four of four, three of four, and two of three flaps were stable in vivo and under negative pressure. Flaps that demonstrated instability had granulation, dehiscence, and poor healing. These occurred in 1 of 6 animals in the traditional RDF group and in 2 of 11 animals in the implant groups. In addition, 13 of 24 animals assigned to the implant groups died, compared with 2 of 8 of those in the traditional RDF group. CONCLUSIONS: The RDF is stable and maintains the airway under physiological conditions. Support materials did not improve stability, render flap harvest more difficult, or increase morbidity and mortality.

The effects of cyclosporin A on transplanted rat allografts.

Since 1983, Cyclosporin A (CsA) has been the most successful primary drug in preventing rejection of organ transplants. This study was designed to determine the efficacy and dose response of CsA in preventing rejection of LBNF-1 rat allografts to Lewis recipients. Four groups of animals were studied. Group I served as the control, and groups II, III, and IV were given daily intramuscular doses of CsA for 1 month. The groups were given doses of 5 mg/kg, 7.5 mg/kg, and 10 mg/kg, respectively. Sixty-eight animals were transplanted to get eight viable transplanted animals at 1 month in each CsA group. Laryngeal viability was assessed with both clinical and histological parameters. Groups II, III, and IV had representative clinically viable larynges. The histology varied and had some correlation with CsA dosage. Group II evidenced changes ranging from mild to severe rejection. Group III was more homogeneous with the most severe change being characterized as mild-to-moderate rejection. Group IV was the most uniform with all representative specimens showing only limited infiltration of inflammatory cells with intact mucosa and submucosal glands (mild rejection). None of the CsA groups evidenced the squamous metaplasia characteristic of the control group. CsA can prevent rejection of laryngeal allografts from LBNF-1 donors to Lewis recipients.

An unusual foreign body of the tongue masquerading as malignancy.

Foreign bodies within the tongue are a rare finding. The history is often not helpful as it is usually remote. Presented is a case of an unusual foreign body in the tongue which masqueraded as a malignancy. The differential diagnosis of an asymptomatic tongue swelling or tongue pain should include foreign body.

Can topical mitomycin prevent laryngotracheal stenosis?

OBJECTIVES/HYPOTHESIS: Early topical application of mitomycin to a laryngotracheal lesion may prevent or reduce laryngotracheal stenosis (LTS). STUDY DESIGN: Prospective controlled animal study. METHODS: LTS was induced in 60 dogs randomly assigned to four groups. Controls received an immediate topical application of normal saline. The suction-control group received an immediate application of normal saline followed by suction of secretions on day 2. The mitomycin group received immediate application of 0.7 mL mitomycin (0.2 mg/mL). The repeat-mitomycin group received an immediate application of mitomycin and a second application on day 2, after secretions were suctioned. The laryngeal lumens were measured endoscopically at baseline, day 12, and day 21. Animals were euthanatized if stenosis approximated 95% or at day 21. RESULTS: All dogs in the mitomycin groups survived to day 21, compared with 12 in the suction group and only 2 controls. No side effects of mitomycin were observed. At day 21, surviving controls had 85% and 95% stenosis. In the mitomycin group, median stenosis was 27% (interquartile range, 29% to 42%); in the repeat-mitomycin group, 30% (22% to 40%); and in the suction-control group, 84.5% (72.5% to 93.5%). The mitomycin group differed significantly from controls on day 12 (median difference = 85%, 95% CI = 80%-94%, P < .0001) and day 21 (difference = 63.9%, 95% CI = 58%-85%, P = .031). CONCLUSION: A single topical application of mitomycin significantly reduces the severity of LTS in dogs. Reapplication after 2 days does not improve results. Prospective clinical studies are warranted to assess the efficacy in humans.

The effects of anesthesia on middle-ear effusions.

Surgeons occasionally note a discrepancy between preoperative assessment of middle-ear effusion and operative observation during the placement of ventilating tubes in children's ears. This study was designed to determine whether this variance is secondary to the effects of inhalation anesthesia or misinterpretation of the preoperative exam. Observations were recorded by three distinctly different methods of measurement: the surgeon, the MD-2 Impedance Analyzer, and the Acoustic Otoscope immediately before and after induction of anesthesia. These results were then analyzed and compared with the operative findings. Anesthetic induction was shown to cause alteration in the presence of middle-ear fluid in less than 10% of cases.

Contraction patterns of intrinsic laryngeal muscles induced by orderly recruitment in the canine.

The specific performance of intrinsic laryngeal muscles has been difficult to evaluate, especially in living subjects. To reproduce natural contractions, we artificially induced orderly recruitment of their innervating axons according to the size principle. In 5 dogs, both recurrent laryngeal nerves (RLNs) were stimulated with 50 through 10 Hz, 300 to 1000 microA currents while 600 Hz, 1000 to 0 microA decreasing blocking currents were administered. Surface electromyography electrodes placed on the thyroarytenoid, posterior cricoarytenoid, and lateral cricoarytenoid muscles were used to determine the amplitudes (in mA) of compound muscle action potentials. There was a highly statistically significant difference (P<.004) between the thyroarytenoideus which had the fastest rate of recruitment (8.38%), and posterior cricoarytenoideus, which had the slowest (4.81%). There was an intermediate recruitment rate (6.72%) of the lateral cricoarytenoideus, a divergence attributed to a more equal distribution in fast and slow types of myofibers and a smaller sample. We submit that RLN axons can be recruited in an orderly manner according to their sizes and that the rates are unique to the muscle classes they innervate. The parameters defining these contraction patterns may offer key information for laryngeal pacing.

An assessment of grafts in the posterior cricoid lamina.

Subglottic stenosis is a recognized complication of prolonged intubation. To date, there is no uniformly successful operative procedure for severe subglottic stenosis, fulfilling the criteria of decannulation and a serviceable voice. The surgical ideals for such a procedure should include the use of autogenous grafting material, avoidance of internal stenting, and limited manipulation of the mucosa. This study was intended to assess the fate of isolated hyoid and thyroid alar grafts interposed in the posterior cricoid lamina. Additionally, anterior/posterior splits with and without anterior grafting were evaluated. Seventeen dogs were used in the determinate animal model. Vocal cord mobility was evaluated by direct laryngoscopy prior to sacrifice. Graphic gross anatomical specimens depict the effects of anterior/posterior splitting on the cricoid cartilage. Clinical correlations are suggested.