Adult presentation of a tracheoesophageal fistula with co-existing laryngeal cleft.

Congenital posterior laryngeal clefts are rare anomalies, being first described by Richter in 1792, and first operated upon successfully by Pettersson in 1955. Most clefts present within the first few months of life, with only a few cases being documented as presenting in adulthood. We present the case of a 50-year-old lady presenting with a previously undiagnosed posterior laryngeal cleft with an associated tracheoesophageal fistula. The defect was graded as 2 on the Benjamin and Inglis classification system of posterior laryngeal clefts. Following a literature review, we believe that our patient is the oldest to present with this congenital defect.

Efficacy of external fixation following nasal manipulation under local anaesthesia.

Nasal fractures are one of the commonest reasons for patients being referred to ENT departments, but few studies have been published about the management of this condition. In particular, the efficacy of external splintage following manipulation has not been assessed. This was a prospective randomized study, which examined the results of manipulation under local anaesthetic and the benefit to be gained from external fixation with Plaster of Paris (POP) following this procedure. Accurate measurements of the degree of deviation of the nose pre- and post-manipulation were obtained using a camera mounted on a specially designed frame. Thirty-three out of 241 consecutive patients seen at a research clinic over the course of 12 months were included in the study. The mean deviation of the nasal bridge at presentation was 4.12 mm. Manipulation under local anaesthetic significantly improved the degree of deviation (mean 2.47 mm, P = 0.0011, 90% CI, 1-2 mm). Randomization of the patients, following manipulation, into POP/none-POP groups showed that external splintage of the nose appeared to be of little practical benefit.

Do positive resection margins after ablative surgery for head and neck cancer adversely affect prognosis? A study of 352 patients with recurrent carcinoma following radiotherapy treated by salvage surgery.

It is generally accepted by surgeons that failure to eradicate malignant disease at the primary site has an adverse effect on survival. The present study investigates 352 patients with squamous carcinoma of the head and neck treated by primary radical radiotherapy and who subsequently underwent surgical ablation for a recurrent carcinoma. A total of 303 (86%) patients had a negative resection margin and 49 (14%) had a positive resection margin. Oral carcinoma was 1.7 times more likely to be associated with a positive margin than other tumours (P = 0.0292). Actuarial calculations demonstrated that 47% of patients with negative margins and 66% of patients with positive margins developed a primary site recurrence (P = 0.0286). Neck node recurrence occurred in 10% of those patients with negative margins and 12% of patients with positive margins. Patients with positive margins had a significantly poorer survival than those with negative margins (P = 0.022). Multivariate analysis failed to confirm any independent adverse effect from a positive margin. The 5 year tumour-specific survival of patients with a positive margin was poorer by 12% than for those patients with a negative margin. The pattern of failure differed between the two groups, with patients having positive margins tending to die of local recurrence.

Sodium metabisulphite causes epithelial damage and increases sheep tracheal blood flow and permeability.

Inhaled sodium metabisulphite (MBS) causes bronchoconstriction, cough and microvascular leakage. We have studied its effects on tracheal blood flow, potential difference (PD) and the permeability from tracheal lumen to venous blood of a low molecular weight hydrophilic tracer, 99mtechnetium-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA) in anaesthetized sheep. Flow was measured in tracheal artery and blood from a cannulated tracheal vein collected for 5 min periods. The tracheal lumen was filled with Krebs-Henseleit solution (KH) containing 99mTc-DTPA for six to eight 15 min periods. During the third or fourth period, MBS (1, 20 or 100 mM) was washed into the tracheal lumen for 15 min. MBS increased tracheal blood flow (venous flow (Q'v), 5-10 min MBS exposure period: 1 mM -9 +/- 18% (n = 3); 20 mM +16 +/- 5% (n = 5; p < 0.05); 100 mM +43 +/- 13% (n = 5; p < 0.05). It decreased PD in a concentration-dependent way. Venous 99mTc-DTPA concentration increased progressively to +266 +/- 176 and +958 +/- 321% 25-30 min after exposure to 20 and 100 mM MBS, respectively (p < 0.05 for both). These effects were not blocked by luminal frusemide (3-7 mM) or flurbiprofen (100-500 microM). Histological sections showed changes to the epithelial cells and large intercellular spaces. Thus, luminal sodium metabisulphite increases tracheal blood flow, reduces transmural potential difference and causes tracheal epithelial damage, leading to an increase in 99mTc-labelled diethylenetriamine penta-acetic acid permeability.

Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep.

Epithelial damage greatly increases the flux of a low molecular weight tracer 99mtechnetium-diethylenetriamine penta-acetic acid (99mTc-DTPA) from tracheal lumen to venous-blood in anaesthetized sheep. We have now investigated whether epithelial damage induced by the detergent, Triton X-100, alters the effects of luminal histamine on blood flow and 99mTc-DTPA flux. The cervical trachea was filled with Krebs-Henseleit solution containing 99mTc-DTPA. Tracheal arterial flow was measured and tracheal venous blood collected. The lumen was exposed to 100 microM histamine on two occasions (Hist 1 and Hist 2) for 15 min. In six out of 11 sheep, the lumen was also exposed to 0.2% Triton X-100 between Hist 1 and Hist 2. Triton X-100 increased the baseline 99mTc-DTPA permeability coefficient from -5.3 x 10(-7) to -400 +/- 130 x 10(-7) cm.s-1. After epithelial damage, Hist 2 produced significantly greater changes in arterial and venous flows than Hist 1 (n = 5) (0-5 min: Hist 1 Q1a = +6.4 +/- 0.8%, Q1v = +6.2 +/- 6.2%; Hist 2 Q1a = +36.7 +/- 12.2%, Q1v = +35.4 +/- 8.8%). Similar changes did not occur in the controls. Venous 99mTc-DTPA concentration during Hist 2 after epithelial damage (0-5 min -37.7 +/- 6.9%) was significantly different from Hist 1 (+5.2 +/- 7.0%). Thus, after epithelial damage, luminal histamine produces more rapid and larger changes in blood flow and a greater reduction in venous 99mTc-DTPA concentration.

Tracheal epithelial damage alters tracer fluxes and effects of tracheal osmolaity in sheep in vivo.

Tracheal osmolaity affects blood flow and the flux of a tracer, technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), from tracheal lumen to venous blood in anesthetized sheep. Hyperosmolar liquids increase blood flow and slightly decrease 99mTc-DTPA flux, whereas hyposmolar liquids have no effect on blood flow and greatly increase 99mTc-DTPA flux. We have now investigated whether epithelial damage induced by exposure of the tracheal lumen to a detergent (0.2% Triton X-100) alters these effects. A tracheal artery was perfused, and tracheal venous blood was collected. The initial tracheal volume was 12.8 +/- 0.7 ml. Triton X-100 greatly increased the permeability coefficient for 99mTc-DTPA from -2.1 x 10(-7) to -240 x 10(-7) cm/s. Hyperosmolar Krebs-Henseleit solution (KH; 739 +/- 6 mosmol/kg) increased arterial (+14.3%) and venous (+21.5%) flows and decreased 99mTc-DTPA output by 51.7%. Water flux into the lumen (+0.3 +/- 0.1 ml) was not significant, and the osmolality decreased by 99 +/- 9 mosmol/kg. Hyposmolar KH (124 +/- 2 mosmol/kg) had no effect on arterial and venous flows (-1.3% for both), and the increase in 99mTc-DTPA output (+8.3%) was small and not significant. The volume decreased by 0.4 +/- 0.1 ml, and the osmolaity increased by 36 +/- 4 mosmol/kg. Thus epithelial damage greatly increases the baseline permeability of the tracheal wall to 99mTc-DTPA. It does not alter the qualitative effects of hypersomolar KH on blood flow and 99mTc-DTPA output but does reduce the effect of hyposmolar KH on 99mTc-DTPA output. The latter effect may be a consequence of the reduced net water movement in response to non-isosmolar solutions after epithelial damage.

Osmolality alters tracheal blood flow and tracer uptake in anesthetized sheep.

Changes in the osmolality of airway surface liquid cause bronchoconstriction, mucus secretion, and ion transport, but little is known about the effects on the permeability of the trachea to drugs applied to the tracheal lumen. Using the anesthetized sheep, we have investigated the effects of hyperosmolar (725 +/- 11 mosmol/kg) and hyposmolar (128 +/- 5 mosmol/kg) Krebs-Henseleit (KH) solution in the tracheal lumen (mean volume 13.6 ml) on the uptake of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), a low-molecular-mass hydrophilic tracer that is thought to cross the epithelium via paracellular pathways, and on blood flow. All changes in osmolality were made by altering the NaCl content. We perfused a tracheal artery and collected tracheal venous blood. Hyperosmolar KH increased water movement into the lumen (+2.0 ml) and solute flux out of the lumen. It increased arterial (+24.5%) and venous (+20.6%) flows and decreased 99mTc-DTPA concentration (-26.3%) and output (-12.0%) in venous blood. Hyposmolar KH caused water movement out of the lumen (-0.9 ml) and solute flux into the lumen. It had no effect on arterial (+0.6%) and venous (+5.5%) flows and greatly increased the concentration (+345%) and output (+375%) of 99mTc-DTPA in venous blood. The baseline permeability coefficient for 99mTc-DTPA (-9.1 x 10(-7) cm/s) was not affected by hyperosmolar KH (-8.7 x 10(-7) cm/s) but was increased by hyposmolar KH (-21.4 x 10(-7) cm/s). These results confirm that hyperosmolar liquid in the lumen increases blood flow and indicate that tracer uptake is affected by the bulk flow of water across the airway wall.

Permeability of ferret trachea in vitro to 99mTc-DTPA and [14C]antipyrine.

Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA; hydrophilic) and [14C]antipyrine ([14C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either 99mTc-DTPA or [14C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline 99mTc-DTPA and [14C]AP permeability coefficients were -4.7 +/- 0.6 (SE) x 10(-7) and -2.2 +/- 0.1 x 10(-5) cm/s, respectively. PAF (10 microM) increased permeability to 99mTc-DTPA to -35.3 +/- 7.6 x 10(-7) cm/s (P < 0.05), but permeability to [14C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 microM), phenylephrine (PE, 100 microM), and albuterol (Alb, 100 microM) caused no change in permeability to 99mTc-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 microM) significantly increased permeability. Abluminal Hist decreased permeability to [14C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to 99mTc-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent.

Tracheal blood flow and luminal clearance of 99mTc-DTPA in sheep.

Tracheal blood flow and 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA) clearance were measured in the sheep trachea in vivo. The tracheal arteries were isolated and perfused. An isolated segment of tracheal lumen was filled with Krebs-Henseleit solution containing 99mTc-DTPA, and radioactivity was measured in blood from a catheterized tracheal vein. Infusions at constant pressure of methacholine (n = 5), albuterol (n = 6), and histamine (n = 5) increased arterial inflow [+250 +/- 73.0, +74.2 +/- 22.9, +68.9 +/- 39.2% (SE), respectively] and venous outflow (+49.5 +/- 13.8, +11.6 +/- 4.5, +6.2 +/- 13.9%) but decreased 99mTc-DTPA output (-36.8 +/- 8.4, -20.4 +/- 6.2, -58.1 +/- 11.7%) and concentration (-53.9 +/- 10.1, -27.3 +/- 7.5, -49.3 +/- 14.4%). Phenylephrine (n = 9) decreased arterial inflow (-49.4 +/- 10.0%) and venous outflow (-4.1 +/- 5.9%) but increased 99mTc-DTPA output (+74.6 +/- 44.2%) and concentration (+94.4 +/- 56.6%). When the tracheal arteries were initially perfused at constant flow and the flow rate was then changed, 50% increases in flow (n = 5) increased perfusion pressure (+35.9 +/- 2.2%) and venous outflow (+10.5 +/- 3.8%) but decreased 99mTc-DTPA output (-24.4 +/- 7.8%) and concentration (-30.4 +/- 8.8%). Decreases in flow of 50% (n = 3) and 100% (n = 10) decreased perfusion pressure (-34.2 +/- 4.2, -80.1 +/- 3.5%, respectively) and venous outflow (-11.0 +/- 4.8, -29.7 +/- 7.2%) but increased 99mTc-DTPA output (+45.9 +/- 27.5, +167.4 +/- 70.4%) and concentration (+64.7 +/- 26.7, +305.7 +/- 110.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in tracheal mucosal thickness and blood flow in sheep.

Airway narrowing may be produced by increasing the blood volume of the airway mucosa. Here changes in tracheal mucosal thickness (MTtr) were measured in 10 anesthetized sheep. Arteries to the cervical trachea were isolated, and blood flow (Qtr) was measured with an electromagnetic flow probe. Simultaneous changes in MTtr were measured with a mechanical probe over a fixed cartilage. Arterial injections of phenylephrine produced dose-related falls in Qtr and MTtr with a maximum peak fall in MTtr of -104 +/- 18 (SE) microns. Methacholine, bradykinin, albuterol, and histamine produced dose-related increases in Qtr. The largest peak increase in MTtr of 308 +/- 121 microns was seen with bradykinin. For methacholine, albuterol, and histamine the largest increases in MTtr were 154 +/- 47, 45 +/- 10, and 153 +/- 31 microns, respectively. The increases in MTtr were not always closely dose related. The peak changes in MTtr occurred substantially later than those in Qtr for all the drugs and up to 120 s later for methacholine and bradykinin. Generally, changes in MTtr and Qtr persisted for less than 10 min; at the higher doses of bradykinin increases in MTtr lasted for up to 15 min. Changes in MTtr were most closely associated in time with changes in Qtr for the vasoconstrictor phenylephrine. These changes in MTtr would alter airway resistance little in the normal trachea and by substantially more in smaller airways such as the bronchi or in the narrowed trachea. Changes in mucosal thickness may be due not only to changes in tracheal blood volume but may also reflect the effects of tissue edema and mucus secretion.

The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep.

The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.