Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.

The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppression of colitis activity and induction of apoptosis, indicating that sIL-6R prevents mucosal T-cell apoptosis. In patients with CD, mucosal T cells showed strong evidence for IL-6 trans signaling, with activation of signal transducer and activator of transcription 3, bcl-2 and bcl-xl. Blockade of IL-6 trans signaling caused T-cell apoptosis, indicating that the IL-6-sIL-6R system mediates the resistance of T cells to apoptosis in CD. These data indicate that a pathway of T-cell activation driven by IL-6-sIL-6R contributes to the perpetuation of chronic intestinal inflammation. Specific targeting of this pathway may be a promising new approach for the treatment of CD.

Adiponectin--its potential to predict and prevent coronary artery disease.

BACKGROUND: Recent evidence suggests that epicardial adipose tissue may contribute locally to the pathogenesis of coronary artery disease (CAD). We investigated how local and systemic adiponectin, an adipokine with anti-inflammatory and insulin sensitizing properties, is related to the presence of CAD and cardiovascular risk factors. METHODS: Serum and adipose tissue samples from subcutaneous and pericoronary depots were collected from sixty consecutive patients with CAD who required coronary artery bypass grafting or patients without CAD who underwent cardiac surgery for aortic valve replacement. Western blot, ELISA and PCR were used to detect and determine the adiponectin concentrations and expression in the samples. RESULTS: Adiponectin concentrations in the serum and pericoronary fat of patients without CAD were significantly higher than in patients with CAD ( P < 0.01). However, the expression of adiponectin mRNA did not differ in any instances. Male gender, BMI > 30 and type 2 diabetes were significantly correlated to decreased serum adiponectin ( P < 0.03). CONCLUSION: Pericoronary fat specifically secretes metabolically active adiponectin. Its local and systemic concentrations are inversely correlated to the presence of coronary artery disease, indicating its anti-atherogenic effects. As for patients with CAD, adiponectin might be a promising marker for intra-individual monitoring of cardiovascular risk factors and thus a course of secondary prevention. Further evaluation is necessary to elucidate whether a novel therapeutic option could be derived against the onset and progression of CAD.

Collapsibility of the internal jugular veins in the lateral decubitus body position: A potential protective role of the cerebral venous outflow against neurodegeneration.

Recent research has revealed that patients with neurodegenerative disease sleep longer in the supine position, while healthy controls prefer sleeping in the lateral decubitus position. Thus, sleeping in the lateral position seems to be protective against neurodegeneration. It has also been suggested that a protective role of this body position could be associated with better cerebral venous drainage in this body position, which results in more active glymphatic system of the brain (the system responsible for clearance of the cerebral tissue from waste products, e.g. amyloid-ß). Since no published evidence exists regarding venous outflow from the cranial cavity in the lateral decubitus position, we performed a pilot sonographic study of the internal jugular veins in 3 young healthy volunteers and 2 patients presenting with abnormal jugular valves. In all healthy volunteers both internal jugular veins were opened in the supine position and collapsed in the sitting one. In the right lateral decubitus position the right internal jugular vein was opened, while the left one was partially collapsed; and-vice versa-in the left lateral decubitus position the right internal jugular vein was partially collapsed and the left one opened. In patients with abnormal jugular valves both internal jugular veins were opened in both lateral decubitus body positions. We hypothesize that in the lateral decubitus body position, because of decreased flow resistance in the extracranial veins, cerebral venous outflow is optimal, which in turn optimizes the activity of the glymphatic system. Therefore, people intuitively prefer this body position during sleep, while other positions are associated with a higher risk of neurodegenerative disorders. Yet, it should be emphasized that our results need to be interpreted with caution, since only a few individuals have been assessed and this discovery should be confirmed in more patients and healthy controls, and by precise quantitative measurements.

Evidence for the transformation of seminoma to yolk sac tumor, with histogenetic considerations.

Recent ultrastructural, cytogenetic, and ploidy analyses indicate that seminoma acts as a precursor from which other forms of testicular germ cell tumor may originate. Ten cases of primary or metastatic testicular germ cell tumors were investigated that showed possible transformation of seminoma to yolk sac tumor. Such transformation was identified in six cases in which foci of abrupt change from seminoma to various patterns of yolk sac tumor occurred, often at the periphery of otherwise pure lobules of seminoma. Immunostains for cytokeratins, placental-like alkaline phosphatase, and alpha-fetoprotein demonstrated the expected changes in reactivity at the foci of such transformation. Four additional cases were regarded as either seminomas with artifactual microcystic change or the close association of seminoma and yolk sac tumor but lacking evidence for transformation. These data support the theory that seminoma is not an "endpoint" neoplasm but may serve a precursor role in the progression to nonseminomatous germ cell tumors.

Independent effects of estradiol on water and food intake.

Six experiments examined the effects of estradiol on ingestive behaviors of guinea pigs. Estradiol treatment was found to reduce water intake independently of its actions on food intake and body weight. In the first experiment, minimum intake and body weight of intact female guinea pigs coincided with rupture of the vaginal membrane, the estimated time of ovulation. In a second experiment, injections of 3 micrograms of estradiol benzoate per day to ovariectomized females significantly depressed food intake, water intake, and body weight, compared with oil injections. The ratio of water intake per gram of food intake did not change significantly during the estrous cycle or following estradiol injections, results suggesting that the reduced drinking might be a consequence of the reduced feeding. However, reducing food rations to 30% below ad lib levels in Experiment 3 by itself had no significant effect on drinking. In Experiment 4, therefore, ovariectomized females were first placed on a food ration 30% below ad lib levels and then injected daily with either 3 micrograms of estradiol benzoate or oil. Compared with oil injections, these estradiol injections significantly reduced water intake, while food intake did not decline significantly. In these experiments, the reduction in food intake was therefore neither a sufficient nor a necessary condition for the estradiol-induced suppression of water intake. The last two experiments verified that estradiol has independent actions on feeding. The daily water ration was reduced to 30% below ad lib levels in Experiment 5, with no significant effect on food intake. In the sixth experiment, the water ration was first reduced to 30% below ad lib levels, and then the ovariectomized females were injected with either oil or 3 micrograms of estradiol benzoate per day. With this reduced water ration, the estradiol significantly suppressed food intake while producing only minimal and insignificant changes in water intake. These findings established that estradiol can independently influence water intake and food intake in the guinea pig and thereby indicate that estradiol operates through di different mechanisms to produce these two effects.

Effects of female hormonal condition on body weight of male partners: dependence on testicular factors.

Four experiments explored the short-term effects of female estrous condition or gonadal hormones on male body weight. Body weights of male guinea pigs and their ovulating female partners were initially found to show a significant periovular suppression relative to those of female cagemates that were not ovulating at that time. Similar effects in male rats have been hypothesized to result from postcopulatory increases in circulating testosterone and the conversion of that testosterone to estradiol. For evaluation of the probable role of the guinea pig testes in the observed phenomenon, intact and castrated male guinea pigs were housed with ovariectomized females. Female estrus, induced by injecting the females with estradiol and progesterone, resulted in an immediate decline in body weight of the intact male partners, but the body weight of castrated male partners was unaffected. Additional tests evaluated the direct effects of estradiol and testosterone on body weight of male guinea pigs. Injections of up to 1 mg per day of testosterone propionate were insufficient to produce short-term suppression of body weight in either intact or castrated males. However, treatment of the males with estradiol readily reduced their body weight. Overall, these results are not consistent with the hypothesis that short-term reductions in body weight of mated males result from immediate postcopulatory increases in circulating testosterone. It is suggested that other, possibly more estrogenic, testicular factors may play a role in the observed phenomenon.

Intracranial estradiol in ovariectomized guinea pigs: effects on ingestive behaviors and body weight.

The present study was undertaken to evaluate the effects of intracranial estradiol stimulation on food intake (FI), water intake (WI), and body weight (BWt) of ovariectomized guinea pigs (GPs). Thirty-five GPs were implanted with bilateral guide cannulae aimed at either the ventromedial hypothalamus, paraventricular nucleus (PVN), or preoptic area and then were stimulated unilaterally with cholesterol and estradiol 17-beta, yielding a total of 70 stimulation sites. Across all GPs, estradiol implants significantly reduced FI, WI and BWt relative to implants of cholesterol. The possibility that the behavioral changes observed were due to the peripheral rather than central effects of the implants was evaluated by comparing the results of stimulations which produced vaginal membrane rupture (VMR) to the results of cases without VMR. There were no significant differences between these groups on any of the dependent variables studied, indicating that peripheral estradiol sufficient to induce VMR was neither necessary nor sufficient to account for the behavioral changes. Histological analysis revealed that implants in the ventromedial-arcuate region (VM/ARC) and PVN significantly lowered FI and BWt, with the effects being greatest in the PVN. Placements in other areas, on the average, did not significantly suppress FI or BWt. The effect of central estradiol on WI was more diffuse. No significant effect of implant location was found for the estrogenic suppression of drinking. These findings are the first demonstration that estradiol applied to particular brain areas can lower FI, WI, and BWt of ovariectomized GPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential expression of thyrotropin receptor mRNA in the porcine heart.

Thyrotropin receptor (TSHR) mRNA expression has previously been detected in human heart, suggesting a possible role for the receptor in cardiac function and pathophysiology. In the present study we examined the regional distribution of TSHR mRNA in pig heart to map potential cardiac sites of TSH action. Polyadenylated mRNA extracted from thyroid, atria, ventricles, aorta, coronary arteries, epicardial fat, and purified preparations of atrial and ventricular cardiomyocytes was subjected to reverse-transcriptase polymerase chain reaction (RT-PCR) using primers designed to amplify a 311 base pair (bp) DNA segment of the human TSHR. After reverse transcription of 100 ng mRNA, cDNA was amplified by PCR using TSHR primers and compared by electrophoresis on 2% agarose gels. Relative levels of TSHR cDNA (normalized to glyceraldehyde 3-phosphate dehydrogenase [GAPDH]) were as follows: Coronary arteries, epicardial fat > right atrium > left atrium > right ventricle, aorta > left ventricle, ventricular cardiocytes. In contrast to ventricular cardiocytes, purified atrial cardiocytes expressed levels of TSHR mRNA readily detectable with RT-PCR. These findings demonstrate that TSHR mRNA expression in porcine heart varies regionally, and furthermore suggest that areas of highest expression (coronary arteries, adipose tissue, right atrium) are potential sites for a functional or pathologic role of the TSHR.

Sex differences in the activational effects of gonadal hormones on food intake and body weight.

Estrogens have been shown to decrease, and androgens to increase body weight (BWt) of guinea pigs (GPs). The magnitude of the BWt sex difference shown by intact adult GPs is due primarily to these concurrent, or activational, effects of gonadal steroids. However, a small but significant sex difference in BWt persists in animals gonadectomized at birth, indicating that early hormonal exposure may permanently influence certain steroid sensitive weight regulatory mechanisms in the two sexes. Three experiments were therefore designed to investigate the short term effects of estradiol and testosterone on food intake (FI) and BWt of gonadectomized adult male and female GPs. In the first experiment, GPs gonadectomized in adulthood were given a single injection of 6 micrograms estradiol benzoate (EB). Although EB treatment reduced FI and BWt of both females and males, significantly larger reductions occurred in females. In the second experiment, GPs gonadectomized at birth received treatments of oil or 2 micrograms EB for 7 days. EB treatment also produced significantly larger effects on FI and BWt in the neonatally gonadectomized females. The third experiment involved GPs gonadectomized as adults who were injected with either oil or 1 mg/day testosterone propionate in oil (TP) for 32 days. Compared to changes in oil injected controls, TP produced significantly larger increases in male BWt than female BWt. Therefore, although GPs show only minor sex differences in BWt which might relate to prenatal gonadal hormonal exposure, significant sex differences remain in their responsiveness to the activational effects of gonadal steroids on FI and BWt in adulthood.

Body weight and growth rates throughout the guinea pig pregnancy: evidence for modulation by endogenous estrogens.

Relationships between endocrine state, body weight, and vaginal membrane condition were evaluated in two studies. In the first study, vaginal membrane and body weight of 15 pregnant subjects were monitored from the ovarian cycle of conception through parturition. There was a significant depression in body weight of 13.3 +/- 3.1 g coincident with vaginal membrane rupture at the estimated time of conception. A second instance of vaginal membrane rupture was found to occur during midpregnancy in 14 of the females. At that time, female body weight showed a significant relative decline of 12.9 +/- 2.4 g. In the second study, treatment of ovariectomized females with estradiol benzoate readily produced rupture of the vaginal membrane and suppressed body weight by 17.9 +/- 1.8 g. It is therefore hypothesized that the observed midpregnancy changes in vaginal membrane condition and body weight identify an interval of increased estrogen stimulation sufficient to produce physiological and behavioral effects in pregnant guinea pigs. Such effects are not readily explained by reference to levels of circulating estrogens or progesterone during pregnancy and therefore may reflect changes in plasma or tissue binding of these steroids.

Behavioral consequences of hormonal deprivation on the responsiveness of female rats to estradiol.

Female rats which had been ovariectomized either 7 days earlier (short-term deprivation, N = 11) or 35 days earlier (long-term deprivation, N = 11) were tested for their response to treatments of estradiol benzoate (6.0 micrograms/kg body weight) and progesterone (1.2 mg/kg). The long-term deprived females showed less sexual behavior than females deprived for only 7 days prior to treatment. In particular, lordosis quotients after treatment with estradiol alone were significantly lower in the long-term deprived females, t(20) = 3.194, p less than 0.01. Following a supplemental progesterone injection, the lordosis scores and the number of proceptive behaviors displayed by long-term deprived females were also significantly lower than these measures in short-term deprived females, t(20) = 3.481, p less than 0.01 and t(20) = 3.737, p less than 0.01, respectively. In contrast, the two groups did not differ in the degree to which estradiol treatment suppressed food intake, F(1,20) = 2.306, N.S. Likewise, the changes in water intake and body weight produced by estradiol treatment did not differ significantly between the two groups, F(1,20) = 0.118, N.S. and F(1,20) = 0.452, N.S., respectively. The results obtained from the sex behavior tests are generally consistent with the notion that hormonal deprivation alters the responsivity or sensitivity of female rats to estradiol. However, these changes do not appear to involve a general decline in receptor sensitivity or number, because the ability of estradiol to suppress ingestive behaviors was not diminished in the long-term deprived females.

Body temperature and temperature gradients: changes during the estrous cycle and in response to ovarian steroids.

Rectal temperature, body weight, and vaginal membrane condition were monitored in female guinea pigs in order to determine the pattern and magnitude of changes in these variables across the estrous cycle and as a result of treatment with ovarian hormones. A thermistor probe was used to measure rectal temperatures at depths of 4 and 8 cm and to determine the temperature gradient between these two sites. Data collected across the estrous cycles of 18 intact females were aligned by day of vaginal membrane rupture, the estimated time of ovulation. Compared to measurements during the midluteal phase of the estrous cycle, rectal temperatures increased significantly one to three days prior to vaginal membrane rupture. In addition, a significant periovular decline was observed in the temperature gradient and in body weight. Treatment of ovariectomized females with 3 micrograms estradiol benzoate for 3 days (EB) followed by a single injection of 0.4 mg progesterone on the 4th day (P) led to biphasic changes in temperature. Compared to a control group which received injections of 0.2 ml corn oil vehicle for 4 consecutive days (OIL), EB significantly increased rectal temperature measured at the depth of 4 cm, but had no significant effect on measurements taken at a depth of 8 cm. The temperature difference between these two sites also decreased significantly. Rectal temperatures at both 4 cm and 8 cm sites dropped significantly following injection of progesterone. Ovarian hormones therefore have significant effects on body temperature of guinea pigs, effects which, in combination with other evidence, lead us to suggest that some of the observed temperature variations may be related to estrogen-induced changes in peripheral vasodilation or other mechanisms of heat loss.

Maintenance of target tissue and sexual behavior with dihydrotestosterone in male rats and guinea pigs.

The ability of dihydrotestosterone (DHT) to maintain androgen-sensitive target tissue and masculine sexual behavior was examined in castrated male rats and guinea pigs. Silastic capsules filled with DHT amd implanted subdermally at the time of castration were found to stimulate epididymal tissue in a dose-dependent manner in both species. However, differences were found in the behavioral effectiveness of this steroid. Capsules containing sufficient DHT to maintain peripheral structures were effective in maintaining copulatory behavior of castrated guinea pigs, but not of the similarly treated rats.

Diverse effects of estradiol-17 beta: concurrent suppression of appetite, blood pressure and vascular reactivity in conscious, unrestrained animals.

Evidence from epidemiological and clinical investigations have suggested a relationship between estrogen-containing oral contraceptives and hypertension. The present series of studies, however, documents the ability of estradiol-17 beta, a natural ovarian estrogen, to lower resting blood pressure and pressor responses to norepinephrine in conscious, unrestrained guinea pigs. Arterial measurements were made of resting blood pressure and heart rate, plus pressor responses to intravenous infusions of 1.56 micrograms norepinephrine. Injection of 30 micrograms estradiol-17 beta reduced resting pressures up to 12% and pressor responses up to 20% in the interval from 12 to 48 hours postinjection. The estradiol treatment also significantly and reversibly lowered food intake, water intake, and body weight. These effects could be induced by either 3 or 30 micrograms of estradiol benzoate for up to 4 days if estradiol treatment was continued. Parallel studies indicated that NE-induced contractions of the isolated aorta were markedly reduced by pretreatment with estradiol. These studies indicate that natural ovarian estrogens may reduce blood pressure by reducing the contractility of the arterial smooth muscle.

Changes in the tonotopic map of the dorsal cochlear nucleus following induction of cochlear lesions by exposure to intense sound.

Hamsters were exposed to intense tones (10 kHz) at levels and durations sufficient to cause stereocilia lesions. The purpose was to determine how the tonotopic map of the dorsal cochlear nucleus (DCN) readjusts to loss of receptor sensitivity. Neural population thresholds and tonotopic organization was mapped over the surface of the DCN in normal unexposed animals and those showing tone-induced lesions. The results indicate that cochlear lesions characterized mainly by loss of stereocilia in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization. These expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning are similar to those observed by others in the auditory nerve following acoustic trauma, and thus would seem to have a peripheral origin. Thus, it is not necessary to invoke plastic changes in the cochlear nucleus to explain the changes observed in the tonotopic map.

Nasofrontal duct reconstruction with silicone rubber sheeting for inflammatory frontal sinus disease: analysis of 164 cases.

The authors reviewed their experience in reconstructing the nasofrontal duct with thin silicone rubber sheeting in patients who had chronic inflammatory frontal sinus disease. The 164 patients were divided into four groups. The patients in group 1 had the traditional modified Lynch procedure, while those in group 2 had certain technical variations of the modified Lynch operation. The patients in the other two groups had major technical variations: those in group 3 had a primary osteoplastic flap approach and those in group 4 had revisions of failed osteoplastic flap with fat obliteration operations. Surgical indications included mucopyocele (87 patients), chronic frontal sinusitis (71 patients), osteomyelitis (2 patients), acute sinusitis (2 patients), and subacute sinusitis (2 patients). Follow-up averaged 47 months. At their last clinic visit, 157 patients (96%) were asymptomatic. Forty-six revision procedures were performed in 30 patients (18% of initial cases). There were no major complications. Nasofrontal duct reconstruction using thin silicone rubber sheeting is technically straightforward, safe, and effective.

The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma.

OBJECTIVES: To determine prognostic factors for survival in patients with invasive well-differentiated thyroid carcinoma, specifically examining laryngotracheal invasion as an independent prognostic factor, and to compare types of surgical resection to determine treatment efficacy. DESIGN: Retrospective review of patients with papillary invasive well-differentiated thyroid carcinoma surgically treated over 45 years. SETTING: Academic tertiary care medical center. PATIENTS: A total of 292 patients with invasive well-differentiated thyroid carcinoma were surgically treated between 1940 and 1995. Informed consent was obtained from all patients. Extent and location of tumor invasion were determined. Invasion of larynx and/or trachea occurred in 124 patients (41%). Patterns of invasion and techniques of surgical resection were evaluated. INTERVENTION: Types of surgical resection performed: complete tumor removal (n = 34), "shave" excision (n = 75), and incomplete tumor excision (n = 15). MAIN OUTCOME MEASURES: Cox regression analysis was used to determine significance of prognostic factors for survival; Kaplan-Meier curves were used to evaluate survival. A P value of less than .05 was statistically significant. RESULTS: Patterns of invasion by thyroid carcinoma included direct spread through laryngeal framework into paraglottic space or spread from involved lymph nodes. Laryngotracheal invasion was a significant, independent, prognostic factor for survival (P < .05). Significance was reached when types of resection were compared for all patients (P < .05) as well as for those with laryngotracheal invasion alone (P < .001). CONCLUSIONS: Laryngotracheal invasion was a significant independent prognostic factor for survival (P < .05). When types of surgical resection were compared, the survival rates of patients who underwent shave excision were not different from those of patients who underwent radical tumor resection if gross tumor did not remain (P > .05). Tumors with minimal invasion may be treated by shaving tumor from the aerodigestive tract. Gross intraluminal involvement should be resected completely to prevent complications.

Signal transduction mechanisms in substance P-mediated ciliostimulation.

Substance P is a neuropeptide released by afferent neurons in the respiratory tract during inflammatory reactions. It produces effects on blood vessels, bronchial smooth muscle, nasal glands, and respiratory cilia. We studied the in vitro effect of substance P on the ciliary beat frequency of human adenoid explants and its mechanism of action. Substance P was added to cultured adenoid at concentrations of 10(-10), 10(-8), 10(-6), and 10(-4) mol/L. Ciliary beat frequency was determined with phase-contrast microscopy and microphotometry. Substance P increased ciliary beat frequency a maximum of 11.9% +/- 3.8% (p < 0.01). Diclofenac (10(-6) mol/L) significantly blocked the ciliostimulatory effects of SP (p < 0.022), indicating that prostaglandin synthesis is an intermediate step in the action of substance P on ciliary beat frequency. The L-arginine analogs, NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibit nitric oxide synthesis from L-arginine. L-Arginine analogs (10(-4) to 10(-2) mol/L) inhibited the effect of substance P (p < 0.02 at the higher concentration). This inhibition was reversed by adding L-arginine, demonstrating that nitric oxide production is a required step in substance P-induced ciliostimulation. Substance P stimulates ciliary activity in human nasal mucosa as a result of secondary production and release of endogenous prostaglandins and nitric oxide. It is likely that inflammatory disease processes that stimulate release of substance P and subsequent prostaglandin and nitric oxide production modify mucociliary transport. Pharmacologic modification of substance P and its second messengers may eventually permit regulation of this important defense mechanism and control of neurogenic inflammation.

Surgical management of early-stage hypopharyngeal carcinoma.

There is little consensus regarding the extent of surgical ablation that is needed to attain cure in early-stage hypopharyngeal carcinoma (HPC). To determine effective surgical management of early-stage HPC, we retrospectively reviewed all cases of stage I or stage II HPC treated at our institution between 1970 and 1992. Of 305 patients identified with HPC, 50 (16%) had stage I (N = 13) or stage II (N = 37) cancer at diagnosis. Thirty-seven of the 50 (74%) underwent surgery alone or combined with preoperative or postoperative radiotherapy (RT). Patients were divided into three surgical groups. Group 1 underwent partial pharyngectomy (N = 9), group 2 underwent total laryngectomy and partial pharyngectomy (N = 17), and group 3 underwent total laryngopharyngectomy with cervical esophagectomy and reconstruction (N = 11). Overall and disease-specific survivals were determined from Kaplan-Meier survival analysis. Disease-free 5-year survival in stage I and II HPCs was 40.1%. Univariate analysis showed a statistically significant decrease in survival for patients undergoing partial pharyngectomy when compared with those undergoing more extensive procedures (p < .03). This was confirmed with multivariate loglogistic regression analysis (p < .03) correcting for confounding variables of site and RT. These data suggest that wide resection improves disease-free survival in patients with early-stage HPC.

Acoustic measurement of subglottic stenosis.

A device that determines cross-sectional area (CSA) of the airway by acoustic reflections (Hood, Inc) was used to measure subglottic area. Airway models were made from Plexiglas rings with known internal dimensions similar to clinically encountered stenoses of various lengths and diameters. Acoustic measurements of airway area were made and compared to actual CSA. There is a strong correlation between CSA measured acoustically and the actual area of simulated stenoses. However, when the CSA of the stenosis was < 0.64 cm2, the signal was impaired, resulting in overestimation of the stenotic CSA. In simulated stenoses with a CSA of < 0.38 cm2, acoustic measurement of the CSA beyond the stenotic segment was unreliable. Determination of the origin of stenosis was accurate with this method. The CSA of cadaver airways was also measured acoustically. The CSA 2.0 cm below the glottis of normal airways in males ranged from 1.28 to 2.74 cm2 and in females 0.87 to 1.43 cm2, with means of 2.16 and 1.09 cm2. It appears that acoustic measurement of CSA of subglottic stenosis is a feasible clinical technique that yields dimensions of the airway in situations in which direct measurements are impossible. It was suggested that this technique be used for assessment of subglottic stenosis and evaluation of the efficacy of treatment of subglottic stenosis.