Timeline to dysphagia resolution after endoscopic intervention of an interarytenoid defect based on Video Fluoroscopic Swallow Study dysphagia severity.

INTRODUCTION: We previously reported that endoscopic repair of a Type 1 Laryngeal Cleft (LC1) or Deep Interarytenoid Groove (DIG) improves swallowing function postoperatively. However, caregivers often ask about the timeline to resolution of the need for thickening. This study re-examines this cohort to answer this important caregiver-centered question. METHODS: We reassessed a 3-year retrospective, single-center dataset of children with dysphagia found to have a LC-1 or DIG on endoscopic exam. The primary outcome was rate of complete resolution of dysphagia at 2, 6, and 12 months after endoscopic intervention. A sub-group analysis was made based on severity of dysphagia prior to intervention and by type of endoscopic repair. RESULTS: Thirty-nine patients with mean age 1.35 years that had a LC-1 or DIG met criteria for inclusion. Rate of complete dysphagia resolution increased over time. Those with mild dysphagia (flow-reducing nipple and/or IDDSI consistency 1 or 2) had brisker resolution than those with moderate dysphagia (IDDSI consistency 3 or 4) at 2 months (67% vs 5%, p < 0.01) and at 6 months (80% vs 18%, p < 0.01) after endoscopic repair. There was no difference in dysphagia resolution between patients grouped by type of endoscopic repair. CONCLUSION: Addressing an interarytenoid defect in patients will not result in immediate, complete dysphagia resolution in most patients. However, patients that only require a flow-reducing nipple and/or thickening to an IDDSI consistency 1 or 2 have brisker resolution of the need for thickening than those that require an IDSSI consistency 3 or 4 prior to intervention. These results inform pre-operative discussions of the timeline to resolution based upon severity of dysphagia and help manage caregiver expectations.

Optimal timing and technique for endoscopic management of dysphagia in pediatric aerodigestive patients.

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.

Effects of nicotine on hunger and eating in male and female smokers.

We tested whether the inverse relationship between smoking and body weight may be due in part to nicotine's acute effects on reducing hunger and eating. On four mornings, male and female smokers (n = 10 each), abstinent overnight from smoking and food, received one of three nicotine doses (7.5, 15, and 30 micrograms/kg) or placebo (0) via nasal spray every 30 min for 2 h. Self-reported hunger and satiety ("fullness") and craving for cigarettes were obtained after each dose presentation. Subjects subsequently ate ad lib from a large array of food items varying in sweet taste and fat content. For both males and females, nicotine had no effect on self-reported hunger, but cigarette craving was decreased. Rather than being decreased, caloric intake during the meal was unexpectedly increased following nicotine compared with placebo. Cigarette craving increased after the meal, and this increase was unaffected by nicotine dose. There were virtually no differences between males and females in any effects of nicotine. These results indicate that nicotine may not acutely suppress appetite in fasting smokers and suggest that other actions of nicotine or smoking may account for the lower body weights of smokers.

Effects of nicotine on perceived exertion during low-intensity activity.

Nicotine may decrease perceived exertion during physical work, which may be a potentially reinforcing effect of tobacco smoking. This study examined the effects of nicotine on ratings of perceived exertion (RPE) during low-intensity physical activity representative of activity normally engaged in by adult smokers. Ten male and 10 female smokers participated in four morning sessions, one for placebo and each of three nicotine doses (7.5, 15, and 30 micrograms.kg-1), which were administered by measured-dose nasal spray. Using a bicycle ergometer, subjects exercised at each of two lower power outputs (30 and 60 W) before and after nicotine dosing, while RPE and cardiovascular measures of heart rate and systolic and diastolic blood pressure were obtained. Results indicated no significant effect of nicotine on RPE for either males or females. In contrast, nicotine significantly increased each cardiovascular measure during activity, confirming that cardiovascular responses during exercise do not mediate RPE. Thus, nicotine did not influence perception of exertion during low-intensity physical activity.

The incidence and management of chylous fistulae.

Two hundred neck dissections performed at Toronto General Hospital over a 3 year period are reviewed. There were six intra-operative lymph leaks and five postoperative chylous fistulae. The postoperative chylous fistulae are analysed in detail and the approach to conservative management of lymph leaks is discussed. Two cases required re-exploration of the neck; difficulty in identifying the site of leakage and of sealing lymph channels is discussed. Also reported is the successful use of topical tetracycline powder in two cases and a review of the various treatment modalities advocated in the literature.

Alterations in nasal physiology after laryngectomy: the nasal cycle.

Several changes in nasal physiology have been reported following laryngectomy. This paper reviews these changes and investigates the cycle of alternating distribution of nasal airflow in 20 adults. Information about the cyclic activity was obtained from the areas of condensation formed by nasal expiration on the surface of a Gertner-Podoshin plate. Consecutive measurements of these areas were made at 15-minute intervals during a 6-8 hour period. Five control subjects demonstrated a nasal cyclic activity which was absent in five patients 1-3 years post-laryngectomy. Two patients with preoperative cycles showed none three weeks after laryngectomy. Three patients with a temporary surgical diversion of supraglottic airflow showed cessation of the cycle, which resumed after restoration of the natural airway; one of these patients had undergone hemilaryngectomy with section of both superior laryngeal nerves. Five patients showed no alteration after operation involving no diversion of supraglottic airflow (tonsillectomy). These results demonstrate cessation of the cycle following chronic absence of supraglottic airflow, temporary, cessation during acute absence, and independence of the cycle from superior laryngeal innervation.

The use of topical tetracycline in the management of persistent chylous fistulae.

The management of chylous fistulae remains controversial. A detailed conservative protocol and guidelines regarding surgical intervention are lacking in the literature. This paper presents our experience in the management of two cases of persistent chylous fistulae by successfully employing topical tetracycline. Our regimen of management is discussed and illustrated with the above two cases. An updated review of the pertinent anatomy, physiology, and literature is presented.

The nasal cycle after laryngectomy.

The cycle of alternating distribution of nasal airflow was investigated in 15 adults. Information about cyclic activity was obtained from the areas of condensation formed by nasal expiration on the surface of a Gertner-Podoshin plate. Consecutive measurements of these areas were made at 15 minute intervals during a 6-8 h period. Five control subjects demonstrated a nasal cyclic activity which was absent in 5 patients 1-3 years post laryngectomy. Two patients with preoperative cycles showed none 3 weeks after laryngectomy. Three patients with temporary surgical diversion of supraglottic airflow showed cessation of the cycle, which resumed after restoration of the natural airway; one of these patients had undergone hemilaryngectomy with section of both superior laryngeal nerves. These results demonstrate cessation of the cycle following chronic absence of supraglottic airflow, temporary cessation during acute absence, and independence of the cycle from superior laryngeal innervation.

CT of the nasal cavity.

CT demonstrates nasal anatomy extremely well. The intimate relationship of the nasal cavity to the cerebral, orbital, paranasal sinus, nasopharyngeal, and oral tissues is noted. Examples of benign and malignant neoplasms, inflammatory processes, including intrinsic and extrinsic mass lesions are utilized to demonstrate the value of CT in assessing the nasal cavity in conjunction with its surrounding tissues. Congenital and traumatic lesions also are demonstrated to the same advantage.

Endotoxin-induced tumor necrosis factor.

The serum of BCG-infected mice treated with endotoxin contains a substance (tumor necrosis factor, TNF) which mimics the tumor-necrotizing action of endotoxin itself. TNF is not residual endotoxin, but a factor released from host cells, probably macrophages. TNF induced in the same way in rats and rabbits also causes necrosis of transplanted murine tumors. Unlike endotoxin, TNF is toxic in vitro for neoplastic murine and human cell lines but not for mouse embryo culture. TNF has striking effects on immunologic reactions in vitro, some like those of endotoxin and others unlike those of endotoxin. TNF is a glycoprotein; its molecular weight is less than 70,000. Highly purified preparations do not contain lysosomal or nonlysosomal serum enzymes, interferon or prostaglandin E1.

Metrizamide gradient purification of mouse tumor cells.

A one-step isopycnic density gradient centrifugation procedure is described for purification of highly viable and homogeneous tumor cells from a variety of solid mouse tumors. Mechanically suspended cells are layered onto preformed continuous gradients of medium 199-buffered 7--33% metrizamide (density range 1.05--1.20 g/cu. cm) isoosmotic with mouse plasma and centrifuged for 30 min. Large numbers of tumor cells, generally 85--95% viable and free from 80--95% of contaminating host lymphoid and phagocytic cells and erythrocytes, were consistently recovered from fractionated thymomas, melanomas, and fibrosarcomas. By a variety of criteria, cell surface and other biological properties of gradient-purified tumor cells were normal.

Comparison of antitumor activities of pancreatic ribonuclease and its cross-linked dimer.

The cross-linked dimer of bovine pancreatic RNase (M.W. 28,000) is significantly more effective than the monomer in inhibiting tumor development in mice when administered i.p. 1 day after inoculation with sarcoma 180J ascites cells. Animals bearing solid tumors were not affected. In AKR/J mice with advanced leukemia, a single i.p. injection of 100 mug of the dimer led to about 50% reduction in the enlarged lymph nodes and the spleen at 24 hr. The half-life of the dimer in the bloodstream has been determined to be 10 min in rats and 6 min in mice, compared to values of 5 and 3.5 min, respectively, for the monomer. Analyses of the tissues of untreated leukemic mice for RNase and RNase inhibitors show that the tumor tissues are not deficient in RNase activity. Considerations of possible mechanisms of action of the dimer indicate that other basic proteins in this size range may merit examination as cytostatic agents toward transformed cells.

Partial purification of a serum factor that causes necrosis of tumors.

Tumor necrosis can be induced in transplanted mouse methylcholanthrene-induced sarcoma by a tumor necrosis factor in the serum of mice infected with bacillus Calmette-Guérin and given bacterial endotoxin. Sera from normal mice, endotoxin-treated mice, and mice infected with bacillus Calmette-Guérin do not contain this factor. A 20- to 30-fold purification of the serum factor has been achieved by (NH4)2SO4 fractionation, Sephadex G-100 and G-200 gel filtration, and preparative polyacrylamide electrophoresis. Tumor necrosis factor is not bacterial endotoxin. It migrates with alpha-globulins, is made up of at least four subunits, and has a molecular weight of about 150,000. The active factor is a glycoprotein that contains sialic acid and galactosamine.

An endotoxin-induced serum factor that causes necrosis of tumors.

In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.

Serum-mediated leukemia cell destruction in AKR mice.

AKR mice with spontaneous leukemia were infused with normal serum from a variety of species. Leukemia cell destruction was produced by serum from strains of mice possessing the full spectrum of complement components, but not by serum from strains with a genetically determined deficiency of C5. Serum from guinea pigs, horses, and humans also causes destruction of leukemia cells. The antileukemic factor in normal serum was heat labile (56 degrees C for 35 min) and could be inactivated by cobra venom factor (CVF). Tests of individual complement factors from guinea pig serum and from human serum suggest that C5 is the antileukemic complement component in normal serum. Evidence was obtained that complement also plays a role in the antileukemic effect of interferon and endotoxin.