Mechanisms of gastric distention in esophageal atresia with distal tracheoesophageal fistula.

This paper explains how the chest of the crying infant with the common form of esophageal atresia is a pump for ventilating the distal esophagus and inflating the stomach. Esophageal inflation from the trachea occurs during inspiration and esophageal deflation into the stomach during cry.

Rehabilitation medicine.

This article presents a limited overview of the assistance rehabilitation medicine can offer the elderly surgical patient. Appropriately timed rehabilitation can positively affect surgical outcome of elderly patients by restoring physical abilities and promoting independent function. Specific techniques and programs that follow rehabilitation principles can help offset organ system impairment associated with the aging process itself. Moreover, predictable complications of postoperative bed rest and deconditioning that negatively impact functional mobility and self-care can be prevented or rapidly reversed by adhering to sound rehabilitation precepts. The surgeon should be familiar with the concepts of preserving and restoring function, the members of the rehabilitation team, and the array of programs and settings available for the physically impaired and disabled elderly patient.

Diagnosis of tracheoesophageal fistula by analysis of gastric air.

Two patients receiving positive pressure ventilation experienced marked gaseous abdominal distension. Analysis of gases from the stomach, ventilator, and room air suggested that the gastric gases came from the ventilator in one patient. The diagnosis of tracheoesophageal fistula was confirmed by esophagoscopy. Analysis of gases in the other patient did not support the suspicion of tracheoesophageal fistula, and no fistula was found at autopsy. The technique of gastric air analysis is presented as a simple supporting tool for the clinical diagnosis of tracheoesophageal fistula in patients receiving positive pressure ventilation.

Dysphagia and expiratory air flow.

Expiratory air flow preserves the freedom of the upper airway from foodway contamination in patients with dysphagia. Valving the tracheostomy cannula, "quad coughing," the Heimlich maneuver, the "supraglottic swallow," and coupling to a ventilator each has a place among the measures used for treating aspiration.

Scintigraphy for the detection and quantification of subglottic aspiration: preliminary observations.

Eleven patients with previously documented aspiration underwent a radioisotopic swallowing study to detect and quantify airway penetration. In those subjects able to complete a rapid-acquisition phase during swallowing, no laryngotracheal penetration was seen despite previous evidence of aspiration. However, sequential static pulmonary imaging showed significant aspiration in three individuals. Attempts were made to measure the percentage of ingested material aspirated and the clearance rate from the airways. Eight patients (73%) failed to show definite evidence of aspiration on scintigrams. It is hypothesized that the lack of scintigraphic detection in previously proven aspirators was due either to interval improvement of the dysphagia or to difficult-to-detect laryngotracheal aspiration. Isotopic imaging during swallowing appears to have little utility; however, after ingestion, the technique can demonstrate more distal penetration not detected on videofluoroscopy. More studies are suggested to better define the sensitivity and specificity of scintigraphy in aspiration detection and to determine whether these techniques have prognostic value that could alter patient management.

Using ventilators for speaking and swallowing.

An inflated cuff, although commonly thought to be required for the ventilator-dependent patient with a tracheostomy cannula, precludes speaking and has adverse implications for swallowing. Clinical trials with five ventilator-dependent, cognitively intact individuals with glottic control document that a deflated cuff is compatible with ventilation, preserves oral communication, and restores safe alimentation by mouth.

A novel sorbitol transport mechanism in cultured renal papillary epithelial cells.

The renal papillary epithelial cell line, GRB-PAP1, accumulates sorbitol when grown in a hypertonic (500 mosmol/kgH2O) bathing medium. When the cells are returned to a 300 mosmol/kgH2O medium, they lose their sorbitol rapidly to the bath. Sorbitol movement across the membranes of these cells was investigated by studying the uptake of radioactive sorbitol and related compounds. Sorbitol uptake increased 71-fold when cells grown in 500 mosmol/kgH2O medium were exposed to a 300 mosmol/kgH2O test solution. The magnitude of the permeability increase was proportional to the size of the change in the osmolality of the bathing medium and not the absolute osmolality. Sorbitol uptake was a linear function of medium sorbitol concentration with no sign of saturation at sorbitol concentrations up to 315 mM. Although the permeability of other polyols was increased when the osmolality was reduced, competition between sorbitol and related sugars and polyols could not be demonstrated. Both the increased sorbitol uptake after a decrease in medium osmolality and the decrease to control permeability after return to the original osmolality were complete within 30 s. A wide variety of transport inhibitors and ion substitutions failed to alter the magnitude of the sorbitol permeability increase. The most effective inhibitor was quinidine, 1 mM reducing sorbitol uptake by 73%. The sorbitol permeability increase could also be blocked by reducing the temperature to 0 degrees C. Nonspecific uptake of sorbitol, such as endocytosis, was shown to be of only minor significance. The large increase in sorbitol permeability and subsequent sorbitol efflux enables these cells to withstand large decreases in osmolality without excessive swelling and consequent damage. A similar compensatory mechanism may operate in vivo in the renal papilla during the onset of diuresis.

Electromyography of the pharyngeal musculature: technical considerations.

Thirty-one EMG studies of the pharyngeal musculature using three types of electrodes were performed. Electrode characteristics are compared according to criteria developed specifically for the pharynx; techniques for electrode positioning are described in detail; and technical difficulties encountered in performing these studies are discussed. Needle electrodes were best for analyzing individual potentials. For analyzing the timing of myoelectric activity, we preferred the hooked wire electrode (for palatopharyngeus or cricopharyngeus) or bipolar suction electrode (for pharyngeal constrictors). Pharyngeal electromyography is technically feasible and has a role in studying normal and pathologic processes.

Depolarization-induced alkalinization in proximal tubules. I. Characteristics and dependence on Na+.

We used intracellular pH-sensitive and voltage microelectrodes to examine the effects of depolarization on intracellular pH (pHi) in isolated perfused proximal tubules from the tiger salamander Ambystoma tigrinum. Tubules were depolarized by raising [K+] in the bath (b) or lumen (l), or by adding Ba2+ (1 mM) to the bath or lumen, always in nominally HCO3-free solutions. Increasing [K+]b from 2.5 to 50 mM caused the basolateral membrane to depolarize by an average of 45 mV, and pHi to increase by 0.23 over 3 min. Similar alkalinization was observed when basolateral Ba2+ (1 mM) was used to depolarize the cell at constant extracellular [K+], suggesting that the alkalinization observed during exposure to elevated [K+]b results from depolarization rather than an increase in [K+]b. The initial rate of depolarization-induced alkalinization (DIA) was proportional to the magnitude of the depolarization, regardless of whether tubules were depolarized by elevated [K+]b, elevated [K+]l, or by basolateral Ba2+. An exception was the initial rate of the alkalinization caused by 1 mM luminal Ba2+, which was more than 10-fold greater than that predicted from the depolarization. The voltage and pHi responses to basolateral Ba2+ were smaller in some tubules than others, as were the responses to elevated [K+]l. Tubules with small responses to 1 mM [Ba2+]b had large responses to 50 mM [K+]l, whereas tubules with large responses to 1 mM [Ba2+]b had small responses to 50 mM [K+]l. This variability can be accounted for by differences in the luminal K+ conductance. The DIA was partially inhibited by removal of Na+ from only the lumen or only the bath, but completely inhibited by bilateral Na+ removal. We conclude that the depolarization-induced alkalinization results from additive effects of Na+-dependent processes at both the luminal and basolateral membranes.

Depolarization-induced alkalinization in proximal tubules. II. Effects of lactate and SITS.

Intracellular pH and voltage microelectrodes were used to further characterize the depolarization-induced alkalinization (DIA) observed in isolated perfused proximal tubules of the tiger salamander Ambystoma tigrinum. Tubules were depolarized by raising basolateral [K+] from 2.5 to 50 mM. The solutions were air equilibrated and nominally HCO3- free (estimated [HCO3-] = 0.2 mM). In the preceding study we showed that the DIA is partially blocked by removal of Na+ from only the lumen or only the bath, but completely blocked by bilateral Na+ removal. In the present study we found that bilateral amiloride (1 mM) had no effect on the DIA, suggesting that Na-H exchange is not involved. In contrast, basolateral 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) (0.5 mM) partially blocked the DIA, presumably due to inhibition of one or more of three SITS-sensitive basolateral transporters present in amphibian proximal tubules: electrogenic Na-HCO3 cotransport, Na-dependent Cl-HCO3 exchange, and H-lactate cotransport. Bilateral removal of all organic substrates, or of only lactate (Lac-) also blocked the DIA partially. As shown elsewhere (A. W. Siebens, and W. F. Boron, J. Gen. Physiol. 90: 799-831, 1987), in the absence of depolarization, luminal Lac- causes a pHi increase due to luminal Lac- entry via a Na-Lac cotransporter, followed by basolateral Lac- exit via an H-Lac cotransporter sensitive to alpha-cyano-4-hydroxycinnamate (CHC). Three lines of evidence indicate that this Na-Lac/H-Lac mechanism is involved in the DIA. 1) As noted previously, the DIA is partially blocked by luminal Na+ removal. 2) With the DIA partially blocked by basolateral SITS, removal of Lac- from only the lumen blocks the remainder of the DIA. 3) Basolateral CHC partially blocks the DIA. Our data suggest that the DIA is mediated by at least two additive mechanisms, a basolateral transporter that is SITS sensitive and Na+ dependent, and the Na-Lac/H-Lac transport system.

Bolus position at swallow onset in normal adults: preliminary observations.

A "delayed swallowing reflex/response" (i.e., when the swallow reflex is not triggered when the bolus passes the back of the tongue at the anterior facial arch) Logemann has been widely accepted as an abnormality. Careful review of the literature supports the premise that a "delayed swallowing reflex/response" may in fact be a variation of normal. This paper describes swallowing in normal adults. We report the videofluoroscopic measurements of bolus position at the onset of swallow. A radiopaque marker was affixed to the anterior facial arch and the distance between the head of the bolus and the anterior facial arch was measured at the onset of swallow. A statistically significant proportion of swallows (22 of 30) occurred after the head of the bolus passed the anterior facial arch. This finding suggests that there may be diverse sites for elicitation of the swallowing response/reflex rather than a single site (i.e., the anterior facial arch). The relevance of this finding to treatment using thermal stimulation is discussed, as is the versatility of the normal pharynx.

Motions of the posterior pharyngeal wall in swallowing.

The motions of the posterior pharyngeal wall during swallowing were studied in four asymptomatic males using a new method for videoradiography. Radiopaque markers of 4 mm diameter were affixed to the pharyngeal wall by suction. Ventrodorsal and axial components of motion were measured frame by frame. Large axial motions occurred during the pharyngeal stage of swallowing. Cephalad displacement of each marker occurred early and was followed by caudad motion. Within the pharyngoesophageal segment, there were cephalocaudal motions measuring as much as 25 mm. A late caudad motion beyond the reference position was observed in this segment in two participants. This late motion may play a role in passing the bolus through the pharyngoesophageal segment. The findings support the concept of an "engulfment" mechanism in pharyngeal kinesiology.

Role of monocarboxylate transport in the regulation of intracellular pH of renal proximal tubule cells.

Traditional models of acid-base transport and intracellular pH (pHi) regulation in the renal proximal tubule have been based on the existence of a Na+/H+ exchanger at the luminal membrane and a simple HCO3- conductance at the basolateral membrane. Our recent work, in which we used pH-sensitive microelectrodes or dyes to monitor pHi in isolated renal tubules perfused in the nominal absence of HCO3-, has demonstrated the existence of a novel mechanism of acid extrusion in amphibian and mammalian proximal tubule cells. The salamander proximal tubule, for example, possesses an electroneutral Na+ monocarboxylate (Na+-X-) co-transporter, but only at the luminal membrane. It also possesses an electroneutral H+-X- co-transporter, but only at the blood side or basolateral membrane. In the presence of lactate, the luminal Na+-lactate co-transporter mediates a net influx of lactate, driven by the Na+ gradient. The cell-to-blood lactate gradient, in turn, drives the coupled efflux of H+ and lactate across the basolateral membrane. The net effect is the reabsorption of lactate, the luminal uptake of Na+ and the basolateral extrusion of H+. Acid extrusion mediated by this monocarboxylate system in the salamander is comparable in magnitude to that mediated by the Na+/H+ exchanger. In the S3 segment of the rabbit proximal tubule, a similar monocarboxylate system (studied with acetate instead of lactate) extrudes acetate at twice the rate of the Na+/H+ exchanger. Thus, monocarboxylate transport, at least in the nominal absence of HCO3-, can have a major impact on pHi regulation.

Solute transport and epithelial cell volume regulation.

1. The regulation of epithelial cell volume is an essential requirement for normal tissue function and the maintenance of cellular integrity. 2. Renal papillary epithelial cells utilize an organic to compensate for the shrinkage associated with exposure to hypertonic solutions. 3. These cells synthesize the polyol, sorbitol, to increase their intracellular solute content. 4. Sorbitol is synthesized from glucose by the enzyme aldose reductase; exposure of the cells to hypertonic media causes aldose reductase synthesis and subsequent sorbitol generation over a two or three day period. 5. The intracellular signal for the formation of aldose reductase is not yet identified.

Effect of electroneutral luminal and basolateral lactate transport on intracellular pH in salamander proximal tubules.

We used microelectrodes to examine the effects of organic substrates, particularly lactate (Lac-), on the intracellular pH (pHi) and basolateral membrane potential (Vbl) in isolated, perfused proximal tubules of the tiger salamander. Exposure of the luminal and basolateral membranes to 3.6 mM Lac- caused pHi to increase by approximately 0.2, opposite to the decrease expected from nonionic diffusion of lactic acid (HLac) into the cell. Addition of Lac- to only the lumen also caused alkalinization, but only if Na+ was present. This alkalinization was not accompanied by immediate Vbl changes, which suggests that it involves luminal, electroneutral Na/Lac cotransport. Addition of Lac- to only the basolateral solution caused pHi to decrease by approximately 0.08. The initial rate of this acidification was a saturable function of [Lac-], was not affected by removal of Na+, and was reversibly reduced by alpha-cyano-4-hydroxycinnamate (CHC). Thus, the pHi decrease induced by basolateral Lac- appears to be due to the basolateral entry of H+ and Lac-, mediated by an H/Lac cotransporter (or a Lac-base exchanger). Our data suggest that this transporter is electroneutral and is not present at the luminal membrane. A key question is how the addition of Lac- to the lumen increases pHi. We found that inhibition of basolateral H/Lac cotransport by basolateral CHC reduced the initial rate of pHi increase caused by luminal Lac-. On the other hand, luminal CHC had no effect on the luminal Lac(-)-induced alkalinization. These data suggest that when Lac- is present in the lumen, it enters the cell from the lumen via electroneutral Na/Lac cotransport and then exists with H+ across the basolateral membrane via electroneutral H/Lac cotransport. The net effect is transepithelial Lac- reabsorption, basolateral acid extrusion, and intracellular alkalinization.

Electrogenic Na/HCO3 cotransport across basolateral membrane of isolated perfused Necturus proximal tubule.

This study was undertaken to determine whether the proximal tubule of the mud puppy Necturus maculosus possesses a basolateral Na/HCO3 cotransporter. We examined the effects on basolateral membrane potential (Vbl) and intracellular pH (pHi) of 1) lowering basolateral [HCO3-] at constant PCO2, and 2) replacing Na+ with N-methyl-D-glucamine. Vbl and pHi were measured with Ling-Gerard and liquid-membrane pH microelectrodes, respectively, in isolated tubules perfused in vitro. We found that decreasing basolateral [HCO3-] from 10 mM (pH 7.5) to 2 mM (pH 6.8) resulted in an immediate depolarization of 14.9 mV, and a pHi decrease of 0.35. SITS (4-acetamido-4'-isothiocyanostibene-2,2'-disulfonic acid, 0.5 mM) inhibited the HCO3-induced depolarization by 87% and inhibited the initial rate of the pHi decrease by 79%. Replacement of basolateral Na+ with N-methyl-D-glucamine resulted in an immediate depolarization of 11.3 mV, and a pHi decrease of 0.36. SITS inhibited the zero Na-induced depolarization by 86% and the initial rate of the pHi decrease by 81%. Nominal removal of basolateral HCO3- (replaced with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) inhibited the zero Na-induced depolarization by 64%, whereas nominal removal of Na+ inhibited the 2 mM HCO3-induced depolarization by 67%. Replacement of all basolateral Cl- with glucuronate did not inhibit the changes in Vbl induced by changing [HCO3-] or [Na+]. Observations similar to those described above have been made previously on Ambystoma proximal tubules, and attributed to an electrogenic Na/HCO3 cotransport mechanism that carries HCO3-, Na+, and net negative charge in the same direction. We conclude that Necturus proximal tubules possess a similar, if not identical, electrogenic Na/HCO3 cotransport mechanism.

Achondroplasia: effectiveness of an orthosis in reducing deformity of the spine.

Deformity of the spine and its complications have long been accepted as characteristics of achondroplasia. We have sought to prevent these with a spinal orthosis. This report includes a description of the orthosis and an analysis of its use in achondroplastic children and adults. Nineteen dwarfs between 11 and 52 months of age were fitted with a light truncal polyform orthosis. The effect on the thoracolumbar (TL) and lumbosacral curves (LS) in the seated and standing child were compared by measurements made from lateral roentgenograms with and without the orthosis. The group mean reduction in TL curve of the seated dwarfs was 23 degrees (range 2 degrees to 73 degrees) and the reduction in the LS curve in the standing position was 15 degrees (range 1 degree to 44 degrees). Seventeen older children aged 4-1/2 to 11-2/3 years were equipped with an aluminum version of the orthosis. Their TL curve sitting was reduced by a mean of 31 degrees (range 6 degrees to 45 degrees) and their LS curve standing was decreased by 16 degrees (range 6 degrees to 30 degrees). Thirty-one achondroplastic children and adults were braced for back pain and/or neurologic deficits. Most were relieved of their symptoms to some degree. These and other data lead us to conclude that this form of treatment reduces deformity and alleviates symptoms.